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1. A mutation in IFT43 causes non-syndromic recessive retinal degeneration

Author

Biswas, Pooja, Duncan, Jacque L, Ali, Muhammad, Matsui, Hiroko, Naeem, Muhammad Asif, Raghavendra, Pongali B, Frazer, Kelly A, Arts, Heleen H, Riazuddin, Sheikh, Akram, Javed, Hejtmancik, J Fielding, Riazuddin, S Amer, and Ayyagari, Radha

Subjects
Biological Sciences, Genetics, Rare Diseases, Neurodegenerative, Pediatric, Neurosciences, Eye Disease and Disorders of Vision, Biotechnology, Clinical Research, 2.1 Biological and endogenous factors, Eye, Base Sequence, Carrier Proteins, Consanguinity, Exome, Female, Genes, Recessive, Homozygote, Humans, Male, Mutation, Pedigree, Phenotype, Retina, Retinal Degeneration, Exome Sequencing, Medical and Health Sciences, Genetics & Heredity
Abstract

The aim of this work is to identify the molecular cause of autosomal recessive early onset retinal degeneration in a consanguineous pedigree. Seventeen members of a four-generation Pakistani family were recruited and underwent a detailed ophthalmic examination. Exomes of four affected and two unaffected individuals were sequenced. Variants were filtered using exomeSuite to identify rare potentially pathogenic variants in genes expressed in the retina and/or brain and consistent with the pattern of inheritance. Effect of the variant observed in the gene Intraflagellar Transport Protein 43 (IFT43) was studied by heterologous expression in mIMCD3 and MDCK cells. Expression and sub-cellular localization of IFT43 in the retina and transiently transfected cells was examined by RT-PCR, western blot analysis, and immunohistochemistry. Affected members were diagnosed with early onset non-syndromic progressive retinal degeneration and the presence of bone spicules distributed throughout the retina at younger ages while the older affected members showed severe central choroidal atrophy. Whole-exome sequencing analysis identified a novel homozygous c.100 G > A change in IFT43 segregating with retinal degeneration and not present in ethnicity-matched controls. Immunostaining showed IFT43 localized in the photoreceptors, and to the tip of the cilia in transfected mIMCD3 and MDCK cells. The cilia in mIMCD3 and MDCK cells expressing mutant IFT43 were found to be significantly shorter (P

Published
2017

2. Mutations in the Gene Encoding IFT Dynein Complex Component WDR34 Cause Jeune Asphyxiating Thoracic Dystrophy

Author

Schmidts, Miriam, Vodopiutz, Julia, Christou-Savina, Sonia, Cortés, Claudio R, McInerney-Leo, Aideen M, Emes, Richard D, Arts, Heleen H, Tüysüz, Beyhan, D’Silva, Jason, Leo, Paul J, Giles, Tom C, Oud, Machteld M, Harris, Jessica A, Koopmans, Marije, Marshall, Mhairi, Elçioglu, Nursel, Kuechler, Alma, Bockenhauer, Detlef, Moore, Anthony T, Wilson, Louise C, Janecke, Andreas R, Hurles, Matthew E, Emmet, Warren, Gardiner, Brooke, Streubel, Berthold, Dopita, Belinda, Zankl, Andreas, Kayserili, Hülya, Scambler, Peter J, Brown, Matthew A, Beales, Philip L, Wicking, Carol, UK10K, Duncan, Emma L, and Mitchison, Hannah M

Subjects
Rare Diseases, Pediatric, Underpinning research, 1.1 Normal biological development and functioning, Generic health relevance, Animals, Asians, Axoneme, Carrier Proteins, Child, Chlamydomonas, Cilia, Cytoplasmic Dyneins, Cytoskeleton, Ellis-Van Creveld Syndrome, Exome, Exons, Humans, Infant, Infant, Newborn, Intracellular Signaling Peptides and Proteins, Mutation, Protein Conformation, Proteomics, Whites, UK10K, Asian People, White People, Biological Sciences, Medical and Health Sciences, Genetics & Heredity
Abstract

Bidirectional (anterograde and retrograde) motor-based intraflagellar transport (IFT) governs cargo transport and delivery processes that are essential for primary cilia growth and maintenance and for hedgehog signaling functions. The IFT dynein-2 motor complex that regulates ciliary retrograde protein transport contains a heavy chain dynein ATPase/motor subunit, DYNC2H1, along with other less well functionally defined subunits. Deficiency of IFT proteins, including DYNC2H1, underlies a spectrum of skeletal ciliopathies. Here, by using exome sequencing and a targeted next-generation sequencing panel, we identified a total of 11 mutations in WDR34 in 9 families with the clinical diagnosis of Jeune syndrome (asphyxiating thoracic dystrophy). WDR34 encodes a WD40 repeat-containing protein orthologous to Chlamydomonas FAP133, a dynein intermediate chain associated with the retrograde intraflagellar transport motor. Three-dimensional protein modeling suggests that the identified mutations all affect residues critical for WDR34 protein-protein interactions. We find that WDR34 concentrates around the centrioles and basal bodies in mammalian cells, also showing axonemal staining. WDR34 coimmunoprecipitates with the dynein-1 light chain DYNLL1 in vitro, and mining of proteomics data suggests that WDR34 could represent a previously unrecognized link between the cytoplasmic dynein-1 and IFT dynein-2 motors. Together, these data show that WDR34 is critical for ciliary functions essential to normal development and survival, most probably as a previously unrecognized component of the mammalian dynein-IFT machinery.

Published
2013

4. Mutations in EXTL3 Cause Neuro-immuno-skeletal Dysplasia Syndrome

Author

Oud, Machteld M., Tuijnenburg, Paul, Hempel, Maja, van Vlies, Naomi, Ren, Zemin, Ferdinandusse, Sacha, Jansen, Machiel H., Santer, René, Johannsen, Jessika, Bacchelli, Chiara, Alders, Marielle, Li, Rui, Davies, Rosalind, Dupuis, Lucie, Cale, Catherine M., Wanders, Ronald J.A., Pals, Steven T., Ocaka, Louise, James, Chela, Müller, Ingo, Lehmberg, Kai, Strom, Tim, Engels, Hartmut, Williams, Hywel J., Beales, Phil, Roepman, Ronald, Dias, Patricia, Brunner, Han G., Cobben, Jan-Maarten, Hall, Christine, Hartley, Taila, Le Quesne Stabej, Polona, Mendoza-Londono, Roberto, Davies, E. Graham, de Sousa, Sérgio B., Lessel, Davor, Arts, Heleen H., and Kuijpers, Taco W.

Published
2017
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6. Disruption of the Basal Body Protein POC1B Results in Autosomal-Recessive Cone-Rod Dystrophy

Author

Boldt, Karsten, de Baere, Elfride, Klaver, Caroline C.W., Coppieters, Frauke, Koolen, David A., Lugtenberg, Dorien, Neveling, Kornelia, van Reeuwijk, Jeroen, Ueffing, Marius, van Beersum, Sylvia E.C., Zonneveld-Vrieling, Marijke N., Roosing, Susanne, Lamers, Ideke J.C., de Vrieze, Erik, van den Born, L. Ingeborgh, Lambertus, Stanley, Arts, Heleen H., Peters, Theo A., Hoyng, Carel B., Kremer, Hannie, Hetterschijt, Lisette, Letteboer, Stef J.F., van Wijk, Erwin, Roepman, Ronald, den Hollander, Anneke I., and Cremers, Frans P.M.

Published
2014
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7. Identification of a novel synaptic protein, TMTC3, involved in periventricular nodular heterotopia with intellectual disability and epilepsy

Author

Farhan, Sali M K, Nixon, Kevin C J, Everest, Michelle, Edwards, Tara N, Long, Shirley, Segal, Dmitri, Knip, Maria J, Arts, Heleen H, Chakrabarti, Rana, Wang, Jian, Robinson, John F, Lee, Donald, Mirsattari, Seyed M, Rupar, C Anthony, Siu, Victoria M, Poulter, Michael O, Hegele, Robert A, and Kramer, Jamie M

Published
2017
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8. Exome Capture Reveals ZNF423 and CEP164 Mutations, Linking Renal Ciliopathies to DNA Damage Response Signaling

Author

Chaki, Moumita, Airik, Rannar, Ghosh, Amiya K., Giles, Rachel H., Chen, Rui, Slaats, Gisela G., Wang, Hui, Hurd, Toby W., Zhou, Weibin, Cluckey, Andrew, Gee, Heon Yung, Ramaswami, Gokul, Hong, Chen-Jei, Hamilton, Bruce A., Červenka, Igor, Ganji, Ranjani Sri, Bryja, Vitezslav, Arts, Heleen H., van Reeuwijk, Jeroen, Oud, Machteld M., Letteboer, Stef J.F., Roepman, Ronald, Husson, Hervé, Ibraghimov-Beskrovnaya, Oxana, Yasunaga, Takayuki, Walz, Gerd, Eley, Lorraine, Sayer, John A., Schermer, Bernhard, Liebau, Max C., Benzing, Thomas, Le Corre, Stephanie, Drummond, Iain, Janssen, Sabine, Allen, Susan J., Natarajan, Sivakumar, O’Toole, John F., Attanasio, Massimo, Saunier, Sophie, Antignac, Corinne, Koenekoop, Robert K., Ren, Huanan, Lopez, Irma, Nayir, Ahmet, Stoetzel, Corinne, Dollfus, Helene, Massoudi, Rustin, Gleeson, Joseph G., Andreoli, Sharon P., Doherty, Dan G., Lindstrad, Anna, Golzio, Christelle, Katsanis, Nicholas, Pape, Lars, Abboud, Emad B., Al-Rajhi, Ali A., Lewis, Richard A., Omran, Heymut, Lee, Eva Y.-H.P., Wang, Shaohui, Sekiguchi, JoAnn M., Saunders, Rudel, Johnson, Colin A., Garner, Elizabeth, Vanselow, Katja, Andersen, Jens S., Shlomai, Joseph, Nurnberg, Gudrun, Nurnberg, Peter, Levy, Shawn, Smogorzewska, Agata, Otto, Edgar A., and Hildebrandt, Friedhelm

Published
2012
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10. Genetic and clinical characterization of Pakistani families with Bardet-Biedl syndrome extends the genetic and phenotypic spectrum

Author

Maria, Maleeha, Lamers, Ideke J. C., Schmidts, Miriam, Ajmal, Muhammad, Jaffar, Sulman, Ullah, Ehsan, Mustafa, Bilal, Ahmad, Shakeel, Nazmutdinova, Katia, Hoskins, Bethan, van Wijk, Erwin, Koster-Kamphuis, Linda, Khan, Muhammad Imran, Beales, Phil L., Cremers, Frans P. M., Roepman, Ronald, Azam, Maleeha, Arts, Heleen H., and Qamar, Raheel

Published
2016
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11. CC2D2A Is Mutated in Joubert Syndrome and Interacts with the Ciliopathy-Associated Basal Body Protein CEP290

Author

Gorden, Nicholas T., Arts, Heleen H., Parisi, Melissa A., Coene, Karlien L.M., Letteboer, Stef J.F., van Beersum, Sylvia E.C., Mans, Dorus A., Hikida, Abigail, Eckert, Melissa, Knutzen, Dana, Alswaid, Abdulrahman F., Özyurek, Hamit, Dibooglu, Sel, Otto, Edgar A., Liu, Yangfan, Davis, Erica E., Hutter, Carolyn M., Bammler, Theo K., Farin, Frederico M., Dorschner, Michael, Topçu, Meral, Zackai, Elaine H., Rosenthal, Phillip, Owens, Kelly N., Katsanis, Nicholas, Vincent, John B., Hildebrandt, Friedhelm, Rubel, Edwin W., Raible, David W., Knoers, Nine V.A.M., Chance, Phillip F., Roepman, Ronald, Moens, Cecilia B., Glass, Ian A., and Doherty, Dan

Published
2008
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12. Exome sequencing identifies WDR35 variants involved in sensenbrenner syndrome

Author

Gilissen, Christian, Arts, Heleen H., Hoischen, Alexander, Spruijt, Liesbeth, Mans, Dorus A., Arts, Peer, Lier, Bart van, Steehouwer, Marloes, Reeuwijk, Jeroen van, Kant, Sarina G., Roepman, Ronald, Knoers, Nine V.A.M., Veltman, Joris A., and Brunner, Han G.

Subjects
Codon -- Research, Ectodermal dysplasia -- Genetic aspects, Gene mutations -- Analysis, Genetic engineering -- Analysis, Population genetics -- Research, Biological sciences
Abstract

The exomes of two unrelated cranioectodermal dysplasia (CED) patients were sequenced to identify compound heterozygous mutations in WDR35 as the cause of the disease in each of two patients independently. The results provided insight into the potential use of sequencing the exome of a single sporadic patient to find the causative gene and characterized WDR35 as homologous to TULP4 as an intraflagellar transport component, confirming that sensenbrenner syndrome is a ciliary disorder.

Published
2010

13. Interaction of nephrocystin-4 and RPGRIP1 is disrupted by nephronophthisis or Leber congenital amaurosis-associated mutations

Author

Roepman, Ronald, Letteboer, Stef J.F., Arts, Heleen H., van Beersum, Sylvia E.C., Lu, Xinrong, Krieger, Elmar, Ferreira, Paulo A., and Cremers, Frans P.M.

Subjects
Science and technology
Abstract

RPGR-interacting protein 1 (RPGRIP1) is a key component of cone and rod photoreceptor cells, where it interacts with RPGR (retinitis pigmentosa GTPase regulator). Mutations in RPGRIP1 lead to autosomal recessive congenital blindness [Leber congenital amaurosis (LCA)]. Most LCA-associated missense mutations in RPGRIP1 are located in a segment that encodes two C2 domains. Based on the C2 domain of novel protein kinase C[epsilon] (PKC[epsilon]), we built a 3D-homology model for the C-terminal C2 domain of RPGRIP1. This model revealed a potential [Ca.sup.2+]-binding site that was predicted to be disrupted by a missense mutation in RPGRIP1, which was previously identified in an LCA patient. Through yeast two-hybrid screening of a retinal cDNA library, we found this C2 domain to specifically bind to nephrocystin-4, encoded by NPHP4. Mutations in NPHP4 are associated with nephronophthisis and a combination of nephronophthisis and retinitis pigmentosa called Senior-Loken syndrome (SLSN). We show that RPGRIP1 and nephrocystin-4 interact strongly in vitro and in vivo, and that they colocalize in the retina, matching the panretinal localization pattern of specific RPGRIP1 isoforms. Their interaction is disrupted by either mutations in RPGRIP1, found in patients with LCA, or by mutations in NPHP4, found in patients with nephronophthisis or SLSN. Thus, we provide evidence for the involvement of this disrupted interaction in the retinal dystrophy of both SLSN and LCA patients. retinal degeneration | RPGR protein complex | Senior-Loken | sensorineural disease

Published
2005

14. Exome sequencing identifies DYNC2H1 mutations as a common cause of asphyxiating thoracic dystrophy (Jeune syndrome) without major polydactyly, renal or retinal involvement

Author

Schmidts, Miriam, Arts, Heleen H, Bongers, Ernie M H F, Yap, Zhimin, Oud, Machteld M, Antony, Dinu, Duijkers, Lonneke, Emes, Richard D, Stalker, Jim, Yntema, Jan-Bart L, Plagnol, Vincent, Hoischen, Alexander, Gilissen, Christian, Forsythe, Elisabeth, Lausch, Ekkehart, Veltman, Joris A, Roeleveld, Nel, Superti-Furga, Andrea, Kutkowska-Kazmierczak, Anna, Kamsteeg, Erik-Jan, Elçioğlu, Nursel, van Maarle, Merel C, Graul-Neumann, Luitgard M, Devriendt, Koenraad, Smithson, Sarah F, Wellesley, Diana, Verbeek, Nienke E, Hennekam, Raoul C M, Kayserili, Hulya, Scambler, Peter J, Beales, Philip L, Knoers, Nine VAM, Roepman, Ronald, and Mitchison, Hannah M

Published
2013
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15. C14ORF179 encoding IFT43 is mutated in Sensenbrenner syndrome

Author

Arts, Heleen H, Bongers, Ernie M H F, Mans, Dorus A, van Beersum, Sylvia E C, Oud, Machteld M, Bolat, Emine, Spruijt, Liesbeth, Cornelissen, Elisabeth A M, Schuurs-Hoeijmakers, Janneke H M, de Leeuw, Nicole, Cormier-Daire, Valérie, Brunner, Han G, Knoers, Nine V A M, and Roepman, Ronald

Published
2011
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17. A 132 bp deletion affecting the KCNQ1OT1gene associated with Silver-Russell syndrome clinical phenotype

Author

Gaudet, Marie Véronique, Allain, Eric Pierre, Gallant, Lynne M, Arts, Heleen H, and Ben Amor, Mouna

Abstract

BackgroundImprinting centre 2 (IC2) in the chromosomal region 11p15.5 regulates the monoallelic expression of imprinted genes by differential methylation of paternal and maternal chromosomes. Copy number variants in IC2 are associated with Beckwith-Wiedemann syndrome and Silver-Russell syndrome (SRS). Clinical outcome of IC2 deletions seems to depend on the parental origin of the chromosome, deletion size and inclusion or exclusion of enhancer and promoter regions.ResultsA paternally inherited 132 bp deletion within the KCNQ1OT1gene was found in a proband with an SRS clinical phenotype. The patient’s father and paternal grandmother, who both carry the deletion on their maternal chromosome, are unaffected. Review of other IC2 deletions and their associated clinical presentation was useful in understanding the genetic–phenotypic correlation.ConclusionOnly six cases have been reported with deletions involving exclusively IC2, one being identical to our proband’s 132 bp deletion. Our study, which is based on more extensive segregation data than the previous 132 bp deletion report, confirms the association of this deletion with growth restriction when paternally inherited. Remarkably, even though our patient has the same deletion, he has more pronounced phenotypic features; our findings thus suggest that some degree of clinical variability may be associated with this loss.

Published
2023
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18. An organelle-specific protein landscape identifies novel diseases and molecular mechanisms

Author

Boldt, Karsten, van Reeuwijk, Jeroen, Dougherty, Gerard, Lamers, Ideke J C, Coene, Karlien L M, Arts, Heleen H, Betts, Matthew J, Beyer, Tina, Bolat, Emine, Gloeckner, Christian Johannes, Haidari, Khatera, Hetterschijt, Lisette, Lu, Qianhao, Iaconis, Daniela, Jenkins, Dagan, Klose, Franziska, Knapp, Barbara, Latour, Brooke, Letteboer, Stef J F, Marcelis, Carlo L, Mitic, Dragana, Morleo, Manuela, Oud, Machteld M, Koutroumpas, Konstantinos, Riemersma, Moniek, Rix, Susan, Terhal, Paulien A, Toedt, Grischa, van Dam, Teunis J P, de Vrieze, Erik, Wissinger, Yasmin, Wu, Ka Man, Apic, Gordana, Beales, Philip L, Nguyen, Thanh-Minh T, Blacque, Oliver E, Gibson, Toby J, Huynen, Martijn A, Katsanis, Nicholas, Kremer, Hannie, Omran, Heymut, van Wijk, Erwin, Wolfrum, Uwe, Kepes, François, Davis, Erica E, Texier, Yves, Franco, Brunella, Giles, Rachel H, Ueffing, Marius, Russell, Robert B, Roepman, Ronald, Group, UK10K Rare Diseases, Al-Turki, Saeed, Anderson, Carl, Antony, Dinu, Barroso, Inês, van Beersum, Sylvia E C, Bentham, Jamie, Bhattacharya, Shoumo, Carss, Keren, Chatterjee, Krishna, Cirak, Sebahattin, Cosgrove, Catherine, Danecek, Petr, Durbin, Richard, Fitzpatrick, David, Floyd, Jamie, Horn, Nicola, Reghan Foley, A., Franklin, Chris, Futema, Marta, Humphries, Steve E, Hurles, Matt, Joyce, Chris, McCarthy, Shane, Mitchison, Hannah M, Muddyman, Dawn, Muntoni, Francesco, Willer, Jason R, O'Rahilly, Stephen, Onoufriadis, Alexandros, Payne, Felicity, Plagnol, Vincent, Raymond, Lucy, Savage, David B, Scambler, Peter, Schmidts, Miriam, Schoenmakers, Nadia, Semple, Robert, Mans, Dorus A, Serra, Eva, Stalker, Jim, van Kogelenberg, Margriet, Vijayarangakannan, Parthiban, Walter, Klaudia, Whittall, Ros, Williamson, Kathy, Boldt, K, van Reeuwijk, J, Lu, Q, Koutroumpas, K, Nguyen, Tmt, Texier, Y, van Beersum, Sec, Horn, N, Willer, Jr, Mans, Da, Dougherty, G, Lamers, Ijc, Coene, Klm, Arts, Hh, Betts, Mj, Beyer, T, Bolat, E, Gloeckner, Cj, Haidari, K, Hetterschijt, L, Iaconis, D, Jenkins, D, Klose, F, Knapp, B, Latour, B, Letteboer, Sjf, Marcelis, Cl, Mitic, D, Morleo, M, Oud, Mm, Riemersma, M, Rix, S, Terhal, Pa, Toedt, G, van Dam, Tjp, de Vrieze, E, Wissinger, Y, Wu, Km, Apic, G, Beales, Pl, Blacque, Oe, Gibson, Tj, Huynen, Ma, Katsanis, N, Kremer, H, Omran, H, van Wijk, E, Wolfrum, U, Kepes, F, Davis, Ee, Franco, B, Giles, Rh, Ueffing, M, Russell, Rb, Roepman, R, Boldt, Karsten, Van Reeuwijk, Jeroen, Lu, Qianhao, Koutroumpas, Konstantino, Nguyen, Thanh Minh T., Texier, Yve, Van Beersum, Sylvia E. C., Horn, Nicola, Willer, Jason R., Mans, Dorus A., Dougherty, Gerard, Lamers, Ideke J. C., Coene, Karlien L. M., Arts, Heleen H., Betts, Matthew J., Beyer, Tina, Bolat, Emine, Gloeckner, Christian Johanne, Haidari, Khatera, Hetterschijt, Lisette, Iaconis, Daniela, Jenkins, Dagan, Klose, Franziska, Knapp, Barbara, Latour, Brooke, Letteboer, Stef J. F., Marcelis, Carlo L., Mitic, Dragana, Morleo, Manuela, Oud, Machteld M., Riemersma, Moniek, Rix, Susan, Terhal, Paulien A., Toedt, Grischa, Van Dam, Teunis J. P., De Vrieze, Erik, Wissinger, Yasmin, Wu, Ka Man, Al Turki, Saeed, Anderson, Carl, Antony, Dinu, Barroso, Inê, Bentham, Jamie, Bhattacharya, Shoumo, Carss, Keren, Chatterjee, Krishna, Cirak, Sebahattin, Cosgrove, Catherine, Danecek, Petr, Durbin, Richard, Fitzpatrick, David, Floyd, Jamie, Foley, A. Reghan, Franklin, Chri, Futema, Marta, Humphries, Steve E., Hurles, Matt, Joyce, Chri, Mccarthy, Shane, Mitchison, Hannah M., Muddyman, Dawn, Muntoni, Francesco, O'Rahilly, Stephen, Onoufriadis, Alexandro, Payne, Felicity, Plagnol, Vincent, Raymond, Lucy, Savage, David B., Scambler, Peter, Schmidts, Miriam, Schoenmakers, Nadia, Semple, Robert, Serra, Eva, Stalker, Jim, Van Kogelenberg, Margriet, Vijayarangakannan, Parthiban, Walter, Klaudia, Whittall, Ro, Williamson, Kathy, Apic, Gordana, Beales, Philip L., Blacque, Oliver E., Gibson, Toby J., Huynen, Martijn A., Katsanis, Nichola, Kremer, Hannie, Omran, Heymut, Van Wijk, Erwin, Wolfrum, Uwe, Kepes, Françoi, Davis, Erica E., Franco, Brunella, Giles, Rachel H., Ueffing, Mariu, Russell, Robert B., and Roepman, Ronald

Subjects
Proteomics, 0301 basic medicine, Systems Analysis, DNA Mutational Analysis, lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4], General Physics and Astronomy, Datasets as Topic, methods [Chromatography, Affinity], Sensory disorders Donders Center for Medical Neuroscience [Radboudumc 12], Chromatography, Affinity, Mass Spectrometry, Protein Interaction Mapping, therapy [Ciliopathies], genetics [Ciliopathies], methods [Molecular Targeted Therapy], Molecular Targeted Therapy, Protein Interaction Maps, Multidisciplinary, Cilium, Chemistry (all), abnormalities [Spine], pathology [Ciliopathies], genetics [Muscle Hypotonia], therapy [Muscle Hypotonia], Metabolic Disorders Radboud Institute for Molecular Life Sciences [Radboudumc 6], metabolism [Proteins], isolation & purification [Proteins], physiology [Biological Transport], 3. Good health, Cell biology, Vesicular transport protein, pathology [Dwarfism], metabolism [Cilia], Muscle Hypotonia, ddc:500, pathology [Muscle Hypotonia], pathology [Spine], genetics [Dwarfism], Rare cancers Radboud Institute for Health Sciences [Radboudumc 9], Science, Dwarfism, Exocyst, Biology, Article, General Biochemistry, Genetics and Molecular Biology, Physics and Astronomy (all), 03 medical and health sciences, Intraflagellar transport, Ciliogenesis, Organelle, Humans, Cilia, Biochemistry, Genetics and Molecular Biology (all), Proteins, Biological Transport, General Chemistry, therapy [Dwarfism], Fibroblasts, genetics [Proteins], Ciliopathies, Spine, methods [Protein Interaction Mapping], Renal disorders Radboud Institute for Molecular Life Sciences [Radboudumc 11], 030104 developmental biology, Proteostasis, HEK293 Cells, methods [Proteomics]
Abstract

Cellular organelles provide opportunities to relate biological mechanisms to disease. Here we use affinity proteomics, genetics and cell biology to interrogate cilia: poorly understood organelles, where defects cause genetic diseases. Two hundred and seventeen tagged human ciliary proteins create a final landscape of 1,319 proteins, 4,905 interactions and 52 complexes. Reverse tagging, repetition of purifications and statistical analyses, produce a high-resolution network that reveals organelle-specific interactions and complexes not apparent in larger studies, and links vesicle transport, the cytoskeleton, signalling and ubiquitination to ciliary signalling and proteostasis. We observe sub-complexes in exocyst and intraflagellar transport complexes, which we validate biochemically, and by probing structurally predicted, disruptive, genetic variants from ciliary disease patients. The landscape suggests other genetic diseases could be ciliary including 3M syndrome. We show that 3M genes are involved in ciliogenesis, and that patient fibroblasts lack cilia. Overall, this organelle-specific targeting strategy shows considerable promise for Systems Medicine., Mutations in proteins that localize to primary cilia cause devastating diseases, yet the primary cilium is a poorly understood organelle. Here the authors use interaction proteomics to identify a network of human ciliary proteins that provides new insights into several biological processes and diseases.

Published
2016
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21. Clinical and genetic analyses of a Dutch cohort of 40 patients with a nephronophthisis-related ciliopathy

Author

Stokman, Marijn F., van der Zwaag, Bert, van de Kar, Nicole C.A.J., van Haelst, Mieke M., van Eerde, Albertien M., van der Heijden, Joost W., Kroes, Hester Y., Ippel, Elly, Schulp, Annelien J.A., van Gassen, Koen L., van Rooij, Iris A.L.M., Giles, Rachel H., Beales, Philip L., Roepman, Ronald, Arts, Heleen H., Bongers, Ernie M.H.F., Renkema, Kirsten Y., Knoers, Nine V.A.M., van Reeuwijk, Jeroen, Lilien, Marc R., Stokman, Marijn F., van der Zwaag, Bert, van de Kar, Nicole C.A.J., van Haelst, Mieke M., van Eerde, Albertien M., van der Heijden, Joost W., Kroes, Hester Y., Ippel, Elly, Schulp, Annelien J.A., van Gassen, Koen L., van Rooij, Iris A.L.M., Giles, Rachel H., Beales, Philip L., Roepman, Ronald, Arts, Heleen H., Bongers, Ernie M.H.F., Renkema, Kirsten Y., Knoers, Nine V.A.M., van Reeuwijk, Jeroen, and Lilien, Marc R.

Published
2018

22. Clinical and genetic analyses of a Dutch cohort of 40 patients with a nephronophthisis-related ciliopathy

Author

Child Health, Genetica Klinische Genetica, Genetica Sectie Genoomdiagnostiek, Circulatory Health, Regenerative Medicine and Stem Cells, Nefro Vasculaire Geneeskunde, CMM, Genetica Sectie Research, Genetica, Nefrologie, Stokman, Marijn F., van der Zwaag, Bert, van de Kar, Nicole C.A.J., van Haelst, Mieke M., van Eerde, Albertien M., van der Heijden, Joost W., Kroes, Hester Y., Ippel, Elly, Schulp, Annelien J.A., van Gassen, Koen L., van Rooij, Iris A.L.M., Giles, Rachel H., Beales, Philip L., Roepman, Ronald, Arts, Heleen H., Bongers, Ernie M.H.F., Renkema, Kirsten Y., Knoers, Nine V.A.M., van Reeuwijk, Jeroen, Lilien, Marc R., Child Health, Genetica Klinische Genetica, Genetica Sectie Genoomdiagnostiek, Circulatory Health, Regenerative Medicine and Stem Cells, Nefro Vasculaire Geneeskunde, CMM, Genetica Sectie Research, Genetica, Nefrologie, Stokman, Marijn F., van der Zwaag, Bert, van de Kar, Nicole C.A.J., van Haelst, Mieke M., van Eerde, Albertien M., van der Heijden, Joost W., Kroes, Hester Y., Ippel, Elly, Schulp, Annelien J.A., van Gassen, Koen L., van Rooij, Iris A.L.M., Giles, Rachel H., Beales, Philip L., Roepman, Ronald, Arts, Heleen H., Bongers, Ernie M.H.F., Renkema, Kirsten Y., Knoers, Nine V.A.M., van Reeuwijk, Jeroen, and Lilien, Marc R.

Published
2018

23. The KOUNCIL Consortium: From Genetic Defects to Therapeutic Development for Nephronophthisis

Author

Genetica Sectie Research, Child Health, Nefro Vasculaire Geneeskunde, Circulatory Health, Regenerative Medicine and Stem Cells, Nefrologie, Genetica, Renkema, Kirsten Y, Giles, Rachel H, Lilien, Marc R, Beales, Philip L, Roepman, Ronald, Oud, Machteld M, Arts, Heleen H, Knoers, Nine V A M, Genetica Sectie Research, Child Health, Nefro Vasculaire Geneeskunde, Circulatory Health, Regenerative Medicine and Stem Cells, Nefrologie, Genetica, Renkema, Kirsten Y, Giles, Rachel H, Lilien, Marc R, Beales, Philip L, Roepman, Ronald, Oud, Machteld M, Arts, Heleen H, and Knoers, Nine V A M

Published
2018

24. De novo 14q24.2q24.3 microdeletion including IFT43 is associated with intellectual disability, skeletal anomalies, cardiac anomalies, and myopia

Author

Stokman, Marijn F, Oud, Machteld M, van Binsbergen, Ellen, Slaats, Gisela G, Nicolaou, Nayia, Renkema, Kirsten Y, Nijman, Isaac J, Roepman, Ronald, Giles, Rachel H, Arts, Heleen H, Knoers, Nine V A M, van Haelst, Mieke M, Stokman, Marijn F, Oud, Machteld M, van Binsbergen, Ellen, Slaats, Gisela G, Nicolaou, Nayia, Renkema, Kirsten Y, Nijman, Isaac J, Roepman, Ronald, Giles, Rachel H, Arts, Heleen H, Knoers, Nine V A M, and van Haelst, Mieke M

Published
2016

25. De novo 14q24.2q24.3 microdeletion including IFT43 is associated with intellectual disability, skeletal anomalies, cardiac anomalies, and myopia

Author

Genetica Klinische Genetica, Genetica Sectie Genoomdiagnostiek, Child Health, Regenerative Medicine and Stem Cells, Nefro Vasculaire Geneeskunde, Genetica Groep Van Tintelen, Cancer, Genetica Medische Informatica, Circulatory Health, Genetica, Stokman, Marijn F, Oud, Machteld M, van Binsbergen, Ellen, Slaats, Gisela G, Nicolaou, Nayia, Renkema, Kirsten Y, Nijman, Isaac J, Roepman, Ronald, Giles, Rachel H, Arts, Heleen H, Knoers, Nine V A M, van Haelst, Mieke M, Genetica Klinische Genetica, Genetica Sectie Genoomdiagnostiek, Child Health, Regenerative Medicine and Stem Cells, Nefro Vasculaire Geneeskunde, Genetica Groep Van Tintelen, Cancer, Genetica Medische Informatica, Circulatory Health, Genetica, Stokman, Marijn F, Oud, Machteld M, van Binsbergen, Ellen, Slaats, Gisela G, Nicolaou, Nayia, Renkema, Kirsten Y, Nijman, Isaac J, Roepman, Ronald, Giles, Rachel H, Arts, Heleen H, Knoers, Nine V A M, and van Haelst, Mieke M

Published
2016

26. A novel ICK mutation causes ciliary disruption and lethal endocrine-cerebro-osteodysplasia syndrome

Author

Oud, Machteld M., primary, Bonnard, Carine, additional, Mans, Dorus A., additional, Altunoglu, Umut, additional, Tohari, Sumanty, additional, Ng, Alvin Yu Jin, additional, Eskin, Ascia, additional, Lee, Hane, additional, Rupar, C. Anthony, additional, de Wagenaar, Nathalie P., additional, Wu, Ka Man, additional, Lahiry, Piya, additional, Pazour, Gregory J., additional, Nelson, Stanley F., additional, Hegele, Robert A., additional, Roepman, Ronald, additional, Kayserili, Hülya, additional, Venkatesh, Byrappa, additional, Siu, Victoria M., additional, Reversade, Bruno, additional, and Arts, Heleen H., additional

Published
2016
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27. Mainzer-Saldino Syndrome Is a Ciliopathy Caused by IFT140 Mutations

Author

Perrault, Isabelle, Saunier, Sophie, Hanein, Sylvain, Filhol, Emilie, Bizet, Albane A., Collins, Felicity, Salih, Mustafa A.M., Gerber, Sylvie, Delphin, Nathalie, Bigot, Karine, Orssaud, Christophe, Silva, Eduardo, Baudouin, Véronique, Oud, Machteld M., Shannon, Nora, Le Merrer, Martine, Roche, Olivier, Pietrement, Christine, Goumid, Jamal, Baumann, Clarisse, Bole-Feysot, Christine, Nitschke, Patrick, Zahrate, Mohammed, Beales, Philip, Arts, Heleen H., Munnich, Arnold, Kaplan, Josseline, Antignac, Corinne, Cormier-Daire, Valérie, and Rozet, Jean-Michel

Published
2012
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28. Non-invasive sources of cells with primary cilia from pediatric and adult patients

Author

Ajzenberg, Henry, Slaats, Gisela G, Stokman, Marijn F, Arts, Heleen H, Logister, Ive, Kroes, Hester Y, Renkema, Kirsten Y, van Haelst, Mieke M, Terhal, Paulien A, van Rooij, Iris A, Keijzer-Veen, Mandy G, Knoers, Nine V, Lilien, Marc R, Jewett, Michael A, Giles, Rachel H, Ajzenberg, Henry, Slaats, Gisela G, Stokman, Marijn F, Arts, Heleen H, Logister, Ive, Kroes, Hester Y, Renkema, Kirsten Y, van Haelst, Mieke M, Terhal, Paulien A, van Rooij, Iris A, Keijzer-Veen, Mandy G, Knoers, Nine V, Lilien, Marc R, Jewett, Michael A, and Giles, Rachel H

Published
2015

29. Non-invasive sources of cells with primary cilia from pediatric and adult patients

Author

Genetica, Regenerative Medicine and Stem Cells, Nefro Vasculaire Geneeskunde, Genetica Klinische Genetica, Child Health, Genetica Groep Van Tintelen, Nefrologie patientenzorg, Nefrologie, Ajzenberg, Henry, Slaats, Gisela G, Stokman, Marijn F, Arts, Heleen H, Logister, Ive, Kroes, Hester Y, Renkema, Kirsten Y, van Haelst, Mieke M, Terhal, Paulien A, van Rooij, Iris A, Keijzer-Veen, Mandy G, Knoers, Nine V, Lilien, Marc R, Jewett, Michael A, Giles, Rachel H, Genetica, Regenerative Medicine and Stem Cells, Nefro Vasculaire Geneeskunde, Genetica Klinische Genetica, Child Health, Genetica Groep Van Tintelen, Nefrologie patientenzorg, Nefrologie, Ajzenberg, Henry, Slaats, Gisela G, Stokman, Marijn F, Arts, Heleen H, Logister, Ive, Kroes, Hester Y, Renkema, Kirsten Y, van Haelst, Mieke M, Terhal, Paulien A, van Rooij, Iris A, Keijzer-Veen, Mandy G, Knoers, Nine V, Lilien, Marc R, Jewett, Michael A, and Giles, Rachel H

Published
2015

30. The ciliopathy protein CC2D2A Associates with NINL and functions in RAB8-MICAL3-regulated vesicle trafficking

Author

Bachmann-Gagescu, Ruxandra; https://orcid.org/0000-0002-3571-5271, Dona, Margo, Hetterschijt, Lisette, Tonnaer, Edith, Peters, Theo, de Vrieze, Erik, Mans, Dorus A, van Beersum, Sylvia E C, Phelps, Ian G, Arts, Heleen H, Keunen, Jan E, Ueffing, Marius, Roepman, Ronald, Boldt, Karsten, Doherty, Dan, Moens, Cecilia B, Neuhauss, Stephan C F; https://orcid.org/0000-0002-9615-480X, Kremer, Hannie, van Wijk, Erwin, Bachmann-Gagescu, Ruxandra; https://orcid.org/0000-0002-3571-5271, Dona, Margo, Hetterschijt, Lisette, Tonnaer, Edith, Peters, Theo, de Vrieze, Erik, Mans, Dorus A, van Beersum, Sylvia E C, Phelps, Ian G, Arts, Heleen H, Keunen, Jan E, Ueffing, Marius, Roepman, Ronald, Boldt, Karsten, Doherty, Dan, Moens, Cecilia B, Neuhauss, Stephan C F; https://orcid.org/0000-0002-9615-480X, Kremer, Hannie, and van Wijk, Erwin

Abstract

Ciliopathies are a group of human disorders caused by dysfunction of primary cilia, ubiquitous microtubule-based organelles involved in transduction of extra-cellular signals to the cell. This function requires the concentration of receptors and channels in the ciliary membrane, which is achieved by complex trafficking mechanisms, in part controlled by the small GTPase RAB8, and by sorting at the transition zone located at the entrance of the ciliary compartment. Mutations in the transition zone gene CC2D2A cause the related Joubert and Meckel syndromes, two typical ciliopathies characterized by central nervous system malformations, and result in loss of ciliary localization of multiple proteins in various models. The precise mechanisms by which CC2D2A and other transition zone proteins control protein entrance into the cilium and how they are linked to vesicular trafficking of incoming cargo remain largely unknown. In this work, we identify the centrosomal protein NINL as a physical interaction partner of CC2D2A. NINL partially co-localizes with CC2D2A at the base of cilia and ninl knockdown in zebrafish leads to photoreceptor outer segment loss, mislocalization of opsins and vesicle accumulation, similar to cc2d2a-/- phenotypes. Moreover, partial ninl knockdown in cc2d2a-/- embryos enhances the retinal phenotype of the mutants, indicating a genetic interaction in vivo, for which an illustration is found in patients from a Joubert Syndrome cohort. Similar to zebrafish cc2d2a mutants, ninl morphants display altered Rab8a localization. Further exploration of the NINL-associated interactome identifies MICAL3, a protein known to interact with Rab8 and to play an important role in vesicle docking and fusion. Together, these data support a model where CC2D2A associates with NINL to provide a docking point for cilia-directed cargo vesicles, suggesting a mechanism by which transition zone proteins can control the protein content of the ciliary compartment.

Published
2015

31. The Ciliopathy Protein CC2D2A Associates with NINL and Functions in RAB8-MICAL3-Regulated Vesicle Trafficking

Author

Bachmann-Gagescu, Ruxandra, primary, Dona, Margo, additional, Hetterschijt, Lisette, additional, Tonnaer, Edith, additional, Peters, Theo, additional, de Vrieze, Erik, additional, Mans, Dorus A., additional, van Beersum, Sylvia E. C., additional, Phelps, Ian G., additional, Arts, Heleen H., additional, Keunen, Jan E., additional, Ueffing, Marius, additional, Roepman, Ronald, additional, Boldt, Karsten, additional, Doherty, Dan, additional, Moens, Cecilia B., additional, Neuhauss, Stephan C. F., additional, Kremer, Hannie, additional, and van Wijk, Erwin, additional

Published
2015
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32. Non-invasive sources of cells with primary cilia from pediatric and adult patients

Author

Ajzenberg, Henry, primary, Slaats, Gisela G., additional, Stokman, Marijn F., additional, Arts, Heleen H., additional, Logister, Ive, additional, Kroes, Hester Y., additional, Renkema, Kirsten Y., additional, van Haelst, Mieke M., additional, Terhal, Paulien A., additional, van Rooij, Iris A., additional, Keijzer-Veen, Mandy G., additional, Knoers, Nine V., additional, Lilien, Marc R., additional, Jewett, Michael A., additional, and Giles, Rachel H., additional

Published
2015
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33. Ciliopathies with Skeletal Anomalies and Renal Insufficiency due to Mutations in the IFT-A Gene WDR19

Author

Bredrup, Cecilie, Saunier, Sophie, Oud, Machteld M., Fiskerstrand, Torunn, Hoischen, Alexander, Brackman, Damien, Leh, Sabine M., Midtbø, Marit, Filhol, Emilie, Bole-Feysot, Christine, Nitschké, Patrick, Gilissen, Christian, Haugen, Olav H., Sanders, Jan-Stephan F., Stolte-Dijkstra, Irene, Mans, Dorus A., Steenbergen, Eric J., Hamel, Ben C.J., Matignon, Marie, Pfundt, Rolph, Jeanpierre, Cécile, Boman, Helge, Rødahl, Eyvind, Veltman, Joris A., Knappskog, Per M., Knoers, Nine V.A.M., Roepman, Ronald, and Arts, Heleen H.

Published
2011
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34. A truncating mutation in CEP55 is the likely cause of MARCH, a novel syndrome affecting neuronal mitosis.

Author

Frosk, Patrick, Arts, Heleen H., Philippe, Julien, Gunn, Carter S., Brown, Emma L., Chodirker, Bernard, Simard, Louise, Majewski, Jacek, Fahiminiya, Somayyeh, Russell, Chad, Liu, Yangfan P., Hegele, Robert, Katsanis, Nicholas, Goerz, Conrad, Del Bigio, Marc R., and Davis, Erica E.

Abstract

Background Hydranencephaly is a congenital anomaly leading to replacement of the cerebral hemispheres with a fluid-filled cyst. The goals of this work are to describe a novel autosomal-recessive syndrome that includes hydranencephaly (multinucleated neurons, anhydramnios, renal dysplasia, cerebellar hypoplasia and hydranencephaly (MARCH)); to identify its genetic cause (s) and to provide functional insight into pathomechanism. Methods We used homozygosity mapping and exome sequencing to identify recessive mutations in a single family with three affected fetuses. Immunohistochemistry, RT-PCR and imaging in cell lines, and zebrafish models, were used to explore the function of the gene and the effect of the mutation. Results We identified a homozygous nonsense mutation in CEP55 segregating with MARCH. Testing the effect of this allele on patient-derived cells indicated both a reduction of the overall CEP55 message and the production of a message that likely gives rise to a truncated protein. Suppression or ablation of cep55l in zebrafish embryos recapitulated key features of MARCH, most notably renal dysplasia, cerebellar hypoplasia and craniofacial abnormalities. These phenotypes could be rescued by full-length but not truncated human CEP55 message. Finally, we expressed the truncated form of CEP55 in human cells, where we observed a failure of truncated protein to localise to the midbody, leading to abscission failure and multinucleated daughter cells. Conclusions CEP55 loss of function mutations likely underlie MARCH, a novel multiple congenital anomaly syndrome. This association expands the involvement of centrosomal proteins in human genetic disorders by highlighting a role in midbody function. [ABSTRACT FROM AUTHOR]

Published
2017
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35. Disruption of the Basal Body Protein POC1B Results in Autosomal-Recessive Cone-Rod Dystrophy

Author

Roosing, Susanne, primary, Lamers, Ideke J.C., additional, de Vrieze, Erik, additional, van den Born, L. Ingeborgh, additional, Lambertus, Stanley, additional, Arts, Heleen H., additional, Peters, Theo A., additional, Hoyng, Carel B., additional, Kremer, Hannie, additional, Hetterschijt, Lisette, additional, Letteboer, Stef J.F., additional, van Wijk, Erwin, additional, Roepman, Ronald, additional, den Hollander, Anneke I., additional, Cremers, Frans P.M., additional, Boldt, Karsten, additional, de Baere, Elfride, additional, Klaver, Caroline C.W., additional, Coppieters, Frauke, additional, Koolen, David A., additional, Lugtenberg, Dorien, additional, Neveling, Kornelia, additional, van Reeuwijk, Jeroen, additional, Ueffing, Marius, additional, van Beersum, Sylvia E.C., additional, and Zonneveld-Vrieling, Marijke N., additional

Published
2014
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36. Exome sequencing identifiesDYNC2H1mutations as a common cause of asphyxiating thoracic dystrophy (Jeune syndrome) without major polydactyly, renal or retinal involvement

Author

Schmidts, Miriam, primary, Arts, Heleen H, additional, Bongers, Ernie M H F, additional, Yap, Zhimin, additional, Oud, Machteld M, additional, Antony, Dinu, additional, Duijkers, Lonneke, additional, Emes, Richard D, additional, Stalker, Jim, additional, Yntema, Jan-Bart L, additional, Plagnol, Vincent, additional, Hoischen, Alexander, additional, Gilissen, Christian, additional, Forsythe, Elisabeth, additional, Lausch, Ekkehart, additional, Veltman, Joris A, additional, Roeleveld, Nel, additional, Superti-Furga, Andrea, additional, Kutkowska-Kazmierczak, Anna, additional, Kamsteeg, Erik-Jan, additional, Elçioğlu, Nursel, additional, van Maarle, Merel C, additional, Graul-Neumann, Luitgard M, additional, Devriendt, Koenraad, additional, Smithson, Sarah F, additional, Wellesley, Diana, additional, Verbeek, Nienke E, additional, Hennekam, Raoul C M, additional, Kayserili, Hulya, additional, Scambler, Peter J, additional, Beales, Philip L, additional, Knoers, Nine VAM, additional, Roepman, Ronald, additional, and Mitchison, Hannah M, additional

Published
2013
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39. Mutations in the Gene Encoding IFT Dynein Complex Component WDR34 Cause Jeune Asphyxiating Thoracic Dystrophy

Author

ELÇİOĞLU, HURİYE NURSEL, Schmidts, Miriam, Vodopiutz, Julia, Christou-Savina, Sonia, Cortes, Claudio R., McInerney-Leo, Aideen M., Emes, Richard D., Arts, Heleen H., Tuysuz, Beyhan, D'Silva, Jason, Leo, Paul J., Giles, Tom C., Oud, Machteld M., Harris, Jessica A., Koopmans, Marije, Marshall, Mhairi, Elcioglu, Nursel, Kuechler, Alma, Bockenhauer, Detlef, Moore, Anthony T., Wilson, Louise C., Janecke, Andreas R., Hurles, Matthew E., Emmet, Warren, Gardiner, Brooke, Streubel, Berthold, Dopita, Belinda, Zankl, Andreas, Kayserili, Hulya, Scambler, Peter J., Brown, Matthew A., Beales, Philip L., Wicking, Carol, Duncan, Emma L., and Mitchison, Hannah M.

Subjects
RIB-POLYDACTYLY SYNDROME, OUTER SEGMENT, RETROGRADE INTRAFLAGELLAR TRANSPORT, DNA-SEQUENCING DATA, CYTOPLASMIC DYNEIN-2, PROTEIN, PRIMARY CILIA, CILIOPATHIES, VERTEBRATE PHOTORECEPTORS, DYNC2H1 MUTATIONS
Abstract

Bidirectional (anterograde and retrograde) motor-based intraflagellar transport (IFT) governs cargo transport and delivery processes that are essential for primary cilia growth and maintenance and for hedgehog signaling functions. The IFT dynein-2 motor complex that regulates ciliary retrograde protein transport contains a heavy chain dynein ATPase/motor subunit, DYNC2H1, along with other less well functionally defined subunits. Deficiency of IFT proteins, including DYNC2H1, underlies a spectrum of skeletal ciliopathies. Here, by using exome sequencing and a targeted next-generation sequencing panel, we identified a total of 11 mutations in WDR34 in 9 families with the clinical diagnosis of Jeune syndrome (asphyxiating thoracic dystrophy). WDR34 encodes a WD40 repeat-containing protein orthologous to Chlamydomonas FAP133, a dynein intermediate chain associated with the retrograde intraflagellar transport motor. Three-dimensional protein modeling suggests that the identified mutations all affect residues critical for WDR34 protein-protein interactions. We find that WDR34 concentrates around the centrioles and basal bodies in mammalian cells, also showing axonemal staining. WDR34 coimmunoprecipitates with the dynein-1 light chain DYNLL1 in vitro, and mining of proteomics data suggests that WDR34 could represent a previously unrecognized link between the cytoplasmic dynein-1 and IFT dynein-2 motors. Together, these data show that WDR34 is critical for ciliary functions essential to normal development and survival, most probably as a previously unrecognized component of the mammalian dynein-IFT machinery.

Published
2013

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