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196 results on '"Gassmann, Reto"'

1. Nuclear-enriched protein phosphatase 4 ensures outer kinetochore assembly prior to nuclear dissolution.

Author

Rocha, Helder, Simões, Patrícia, Budrewicz, Jacqueline, Lara-Gonzalez, Pablo, Carvalho, Ana, Dumont, Julien, Desai, Arshad, and Gassmann, Reto

Subjects
Chromosome Segregation, Kinetochores, Microtubules, Mitosis, Phosphoprotein Phosphatases, Spindle Apparatus, Chromosomal Proteins, Non-Histone, Nuclear Envelope, Animals
Abstract

A landmark event in the transition from interphase to mitosis in metazoans is nuclear envelope breakdown (NEBD). Important mitotic events occur prior to NEBD, including condensation of replicated chromosomes and assembly of kinetochores to rapidly engage spindle microtubules. Here, we show that nuclear-enriched protein phosphatase 4 (PP4) ensures robust assembly of the microtubule-coupling outer kinetochore prior to NEBD. In the absence of PP4, chromosomes exhibit extended monopolar orientation after NEBD and subsequently mis-segregate. A secondary consequence of diminished outer kinetochore assembly is defective sister chromatid resolution. After NEBD, a cytoplasmic activity compensates for PP4 loss, leading to outer kinetochore assembly and recovery of chromosomes from monopolar orientation to significant bi-orientation. The Ndc80-Ska microtubule-binding module of the outer kinetochore is required for this recovery. PP4 associates with the inner kinetochore protein CENP-C; however, disrupting the PP4-CENP-C interaction does not perturb chromosome segregation. These results establish that PP4-dependent outer kinetochore assembly prior to NEBD is critical for timely and proper engagement of chromosomes with spindle microtubules.

Published
2023

5. Preventing farnesylation of the dynein adaptor Spindly contributes to the mitotic defects caused by farnesyltransferase inhibitors

Author

Holland, Andrew J, Reis, Rita M, Niessen, Sherry, Pereira, Cláudia, Andres, Douglas A, Spielmann, H Peter, Cleveland, Don W, Desai, Arshad, and Gassmann, Reto

Subjects
Biochemistry and Cell Biology, Biological Sciences, Animals, Carrier Proteins, Cell Cycle Proteins, Chromosomal Proteins, Non-Histone, Chromosome Segregation, Dynactin Complex, Dyneins, Enzyme Inhibitors, Farnesyltranstransferase, Humans, Kinetochores, Microtubule-Associated Proteins, Mitosis, Protein Prenylation, Xenopus, Medical and Health Sciences, Developmental Biology, Biochemistry and cell biology
Abstract

The clinical interest in farnesyltransferase inhibitors (FTIs) makes it important to understand how these compounds affect cellular processes involving farnesylated proteins. Mitotic abnormalities observed after treatment with FTIs have so far been attributed to defects in the farnesylation of the outer kinetochore proteins CENP-E and CENP-F, which are involved in chromosome congression and spindle assembly checkpoint signaling. Here we identify the cytoplasmic dynein adaptor Spindly as an additional component of the outer kinetochore that is modified by farnesyltransferase (FTase). We show that farnesylation of Spindly is essential for its localization, and thus for the proper localization of dynein and its cofactor dynactin, to prometaphase kinetochores and that Spindly kinetochore recruitment is more severely affected by FTase inhibition than kinetochore recruitment of CENP-E and CENP-F. Molecular replacement experiments show that both Spindly and CENP-E farnesylation are required for efficient chromosome congression. The identification of Spindly as a new mitotic substrate of FTase provides insight into the causes of the mitotic phenotypes observed with FTase inhibitors.

Published
2015

10. Identification and characterization of borealin, a novel subunit of the vertebrate chromosomal passenger complex

Author

Gassmann, Reto

Subjects
572.8
Abstract

Borealin is a novel fourth subunit of the vertebrate chromosomal passenger complex containing aurora-B kinase, INCENP, and surviving, which has essential regulatory roles at centromeres and the central spindle in mitosis. Co-immunoprecipitation experiments of endogenous proteins suggest that essential all of surviving, the majority of INCENP, and approximately half of aurora-B are complexed with borealin in mitotic cells. We also detected a sub-complex containing aurora-B and INCENP, but no borealin or surviving. Results from sucrose gradient sedimentation experiments suggest that there are high molecular weight complexes containing chromosomal passengers, which may contain nucleosomes. Binding experiments in vitro revealed a strong direct interaction of borealin with surviving, suggesting that it is the main binding partner of borealin in mitosis. Borealin also binds itself n vitro, and this interaction is detectable in vivo. We investigated the role of borealin within the complex and present evidence that, in contrast to INCENP and surviving, borealin is unlikely to be involved in the regulation of aurora-B kinase activity, but may be the subunit that targets the aurora-B and polo-like kinase 1, another essential mitotic kinase.  Depletion of borealin by RNA interference delays mitotic progression and results in kinetochore-spindle mis-attachments and an increase in bipolar spindles associated with ectopic asters. The extra poles severely disrupt the partitioning of chromosomes in anaphase, revealing an unexpected role for the chromosomal passenger complex in the maintenance of mitotic spindle integrity. These studies have identified novel non-histone components of mitotic chromosomes, one of which, nuclear protein p30, is likely to play a role in centromeric chromatin structure.

Published
2004

19. JIP3 interacts with dynein and kinesin-1 to regulate bidirectional organelle transport

Author

Celestino, Ricardo, Gama, José B, Castro-Rodrigues, Artur F., Barbosa, Daniel J., Rocha, Helder, d'Amico, Ennio A., Musacchio, Andrea, Carvalho, Ana Xavier, Morais-Cabral, João H, Gassmann, Reto, and d’Amico, Ennio A.

Subjects
Cytoplasmic Dyneins, Organelles, Sensory Receptor Cells, Animals, Humans, Kinesins, Nerve Tissue Proteins, Cell Biology, Caenorhabditis elegans, Biologie, Adaptor Proteins, Signal Transducing
Abstract

The MAP kinase and motor scaffold JIP3 prevents excess lysosome accumulation in axons of vertebrates and invertebrates. How JIP3’s interaction with dynein and kinesin-1 contributes to organelle clearance is unclear. We show that human dynein light intermediate chain (DLIC) binds the N-terminal RH1 domain of JIP3, its paralog JIP4, and the lysosomal adaptor RILP. A point mutation in RH1 abrogates DLIC binding without perturbing the interaction between JIP3’s RH1 domain and kinesin heavy chain. Characterization of this separation-of-function mutation in Caenorhabditis elegans shows that JIP3–bound dynein is required for organelle clearance in the anterior process of touch receptor neurons. Unlike JIP3 null mutants, JIP3 that cannot bind DLIC causes prominent accumulation of endo-lysosomal organelles at the neurite tip, which is rescued by a disease-associated point mutation in JIP3’s leucine zipper that abrogates kinesin light chain binding. These results highlight that RH1 domains are interaction hubs for cytoskeletal motors and suggest that JIP3–bound dynein and kinesin-1 participate in bidirectional organelle transport.

Published
2022
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20. Integrative Analysis of the Caenorhabditis elegans Genome by the modENCODE Project

Author

modENCODE Consortium, Gerstein, Mark B., Lu, Zhi John, Van Nostrand, Eric L., Cheng, Chao, Arshinoff, Bradley I., Liu, Tao, Yip, Kevin Y., Robilotto, Rebecca, Rechtsteiner, Andreas, Ikegami, Kohta, Alves, Pedro, Chateigner, Aurelien, Perry, Marc, Morris, Mitzi, Auerbach, Raymond K., Feng, Xin, Leng, Jing, Vielle, Anne, Niu, Wei, Rhrissorrakrai, Kahn, Agarwal, Ashish, Alexander, Roger P., Barber, Galt, Brdlik, Cathleen M., Brennan, Jennifer, Brouillet, Jeremy Jean, Carr, Adrian, Cheung, Ming-Sin, Clawson, Hiram, Contrino, Sergio, Dannenberg, Luke O., Dernburg, Abby F., Desai, Arshad, Dick, Lindsay, Dosé, Andréa C., Du, Jiang, Egelhofer, Thea, Ercan, Sevinc, Euskirchen, Ghia, Ewing, Brent, Feingold, Elise A., Gassmann, Reto, Good, Peter J., Green, Phil, Gullier, Francois, Gutwein, Michelle, Guyer, Mark S., Habegger, Lukas, Han, Ting, Henikoff, Jorja G., Henz, Stefan R., Hinrichs, Angie, Holster, Heather, Hyman, Tony, Iniguez, A. Leo, Janette, Judith, Jensen, Morten, Kato, Masaomi, Kent, W. James, Kephart, Ellen, Khivansara, Vishal, Khurana, Ekta, Kim, John K., Kolasinska-Zwierz, Paulina, Lai, Eric C., Latorre, Isabel, Leahey, Amber, Lewis, Suzanna, Lloyd, Paul, Lochovsky, Lucas, Lowdon, Rebecca F., Lubling, Yaniv, Lyne, Rachel, MacCoss, Michael, Mackowiak, Sebastian D., Mangone, Marco, McKay, Sheldon, Mecenas, Desirea, Merrihew, Gennifer, Miller, David M., Muroyama, Andrew, Murray, John I., Ooi, Siew-Loon, Pham, Hoang, Phippen, Taryn, Preston, Elica A., Rajewsky, Nikolaus, Rätsch, Gunnar, Rosenbaum, Heidi, Rozowsky, Joel, Rutherford, Kim, Ruzanov, Peter, Sarov, Mihail, Sasidharan, Rajkumar, Sboner, Andrea, Scheid, Paul, Segal, Eran, Shin, Hyunjin, Shou, Chong, Slack, Frank J., Slightam, Cindie, Smith, Richard, Spencer, William C., Stinson, E. O., Taing, Scott, Takasaki, Teruaki, Vafeados, Dionne, Voronina, Ksenia, Wang, Guilin, Washington, Nicole L., Whittle, Christina M., Wu, Beijing, Yan, Koon-Kiu, Zeller, Georg, Zha, Zheng, Zhong, Mei, Zhou, Xingliang, Ahringer, Julie, Strome, Susan, Gunsalus, Kristin C., Micklem, Gos, Liu, X. Shirley, Reinke, Valerie, Kim, Stuart K., Hillier, LaDeana W., Henikoff, Steven, Piano, Fabio, Snyder, Michael, Stein, Lincoln, Lieb, Jason D., and Waterston, Robert H.

Published
2010

22. PhasAGE Expert Seminar- Dissecting the contribution of motor-cargo adaptors to microtubule-based transport in neurons

Author

Gassmann, Reto

Subjects
PhasAGE Expert Seminar Series, Endosomes, Lysosomes, Neurological disease, Protein Interaction
Abstract

The PhasAGEExpert Seminarsconsist of a series of talks with speakers from PhasAGE partner’s institutions to promote a successful transfer of knowledge about PhasAGE topics – biomolecular phase separation, aging and age-related diseases.

Published
2021
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28. PHF8 mediates histone H4 lysine 20 demethylation events involved in cell cycle progression

Author

Liu, Wen, Tanasa, Bogdan, Tyurina, Oksana V., Zhou, Tian Yuan, Gassmann, Reto, Liu, Wei Ting, Ohgi, Kenneth A., Benner, Chris, Garcia-Bassets, Ivan, Aggarwal, Aneel K., Desai, Arshad, Dorrestein, Pieter C., Glass, Christopher K., and Rosenfeld, Michael G.

Subjects
Histones -- Physiological aspects -- Research, Cell cycle -- Physiological aspects -- Genetic aspects -- Research, DNA damage -- Physiological aspects -- Research -- Genetic aspects
Abstract

While reversible histone modifications are linked to an ever-expanding range of biological functions (1-5), the demethylases for histone H4 lysine 20 and their potential regulatory roles remain unknown. Here we report that the PHD and Jumonji C (JmjC) domain-containing protein, PHF8, while using multiple substrates, including H3K9me1/2 and H3K27me2, also functions as an H4K20me1 demethylase. PHF8 is recruited to promoters by its PHD domain based on interaction with H3K4me2/3 and controls G1-S transition in conjunction with E2F1,HCF-1 (also known as HCFC1) and SETIA (also known as SETD1A), at least in part, by removing the repressive H4K20me1 mark from a subset of E2F1-regulated gene promoters. Phosphorylation-dependent PHF8 dismissal from chromatin in prophase is apparently required for the accumulation of H4K20me1 during early mitosis, which might represent a component of the condensin II loading process. Accordingly, the HEAT repeat clusters in two non-structural maintenance of chromosomes (SMC) condensin II subunits, N-CAPD3 and N-CAPG2 (also known as NCAPD3 and NCAPG2, respectively), are capable of recognizing H4K20me1, and ChIP-Seq analysis demonstrates a significant overlap of condensin II and H4K20me1 sites in mitotic HeLa cells. Thus, the identification and characterization of an H4K20me1 demethylase, PHF8, has revealed an intimate link between this enzyme and two distinct events in cell cycle progression., We evaluated potential substrates for the putative histone demethylase, PHF8, on mononucleosomes. Flag-tagged PHF8 immunoprecipitated from HEK293T cells was capable of demethylating H4K20me1, H3K9me1/2 and H3K27me2, but had no effects [...]

Published
2010
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32. Affinity Purification of Protein Complexes in C. elegans

Author

Zanin, Esther, primary, Dumont, Julien, additional, Gassmann, Reto, additional, Cheeseman, Iain, additional, Maddox, Paul, additional, Bahmanyar, Shirin, additional, Carvalho, Ana, additional, Niessen, Sherry, additional, Yates, John R., additional, Oegema, Karen, additional, and Desai, Arshad, additional

Published
2011
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37. Integrative Analysis of the Caenorhabditis elegans Genome by the modENCODE Project

Author

Gerstein, Mark B., Lu, Zhi John, Van Nostrand, Eric L., Cheng, Chao, Arshinoff, Bradley I., Liu, Tao, Yip, Kevin Y., Robilotto, Rebecca, Rechtsteiner, Andreas, Ikegami, Kohta, Alves, Pedro, Chateigner, Aurelien, Perry, Marc, Morris, Mitzi, Auerbach, Raymond K., Feng, Xin, Leng, Jing, Vielle, Anne, Niu, Wei, Rhrissorrakrai, Kahn, Agarwal, Ashish, Alexander, Roger P., Barber, Galt, Brdlik, Cathleen M., Brennan, Jennifer, Brouillet, Jeremy Jean, Carr, Adrian, Cheung, Ming-Sin, Clawson, Hiram, Contrino, Sergio, Dannenberg, Luke O., Dernburg, Abby F., Desai, Arshad, Dick, Lindsay, Dosé, Andréa C., Du, Jiang, Egelhofer, Thea, Ercan, Sevinc, Euskirchen, Ghia, Ewing, Brent, Feingold, Elise A., Gassmann, Reto, Good, Peter J., Green, Phil, Gullier, Francois, Gutwein, Michelle, Guyer, Mark S., Habegger, Lukas, Han, Ting, Henikoff, Jorja G., Henz, Stefan R., Hinrichs, Angie, Holster, Heather, Hyman, Tony, Iniguez, Leo A., Janette, Judith, Jensen, Morten, Kato, Masaomi, Kent, James W., Kephart, Ellen, Khivansara, Vishal, Khurana, Ekta, Kim, John K., Kolasinska-Zwierz, Paulina, Lai, Eric C., Latorre, Isabel, Leahey, Amber, Lewis, Suzanna, Lloyd, Paul, Lochovsky, Lucas, Lowdon, Rebecca F., Lubling, Yaniv, Lyne, Rachel, MacCoss, Michael, Mackowiak, Sebastian D., Mangone, Marco, McKay, Sheldon, Mecenas, Desirea, Merrihew, Gennifer, Miller, David M., III, Muroyama, Andrew, Murray, John I., Ooi, Siew-Loon, Pham, Hoang, Phippen, Taryn, Preston, Elicia A., Rajewsky, Nikolaus, Rätsch, Gunnar, Rosenbaum, Heidi, Rozowsky, Joel, Rutherford, Kim, Ruzanov, Peter, Sarov, Mihail, Sasidharan, Rajkumar, Sboner, Andrea, Scheid, Paul, Segal, Eran, Shin, Hyunjin, Shou, Chong, Slack, Frank J., Slightam, Cindie, Smith, Richard, Spencer, William C., Stinson, E. O., Taing, Scott, Takasaki, Teruaki, Vafeados, Dionne, Voronina, Ksenia, Wang, Guilin, Washington, Nicole L., Whittle, Christina M., Wu, Beijing, Yan, Koon-Kiu, Zeller, Georg, Zha, Zheng, Zhong, Mei, Zhou, Xingliang, Ahringer, Julie, Strome, Susan, Gunsalus, Kristin C., Micklem, Gos, Liu, Shirley X., Reinke, Valerie, Kim, Stuart K., Hillier, LaDeana W., Henikoff, Steven, Piano, Fabio, Snyder, Michael, Stein, Lincoln, Lieb, Jason D., and Waterston, Robert H.

Published
2010
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38. Crowning the Kinetochore: The Fibrous Corona in Chromosome Segregation

Author

Kops, Geert J P L, Gassmann, Reto, Kops, Geert J P L, and Gassmann, Reto

Abstract

The kinetochore is at the heart of chromosome segregation in mitosis and meiosis. Rather than a static linker complex for chromatin and spindle microtubules, it is highly dynamic in composition, size, and shape. While known for decades that it can expand and grow a fibrous meshwork known as the corona, it was until recently unclear what constitutes this 'crown' and what its relevance is for kinetochore function. Here, we highlight recent discoveries in fibrous corona biology, and place them in the context of the processes that orchestrate high-fidelity chromosome segregation.

Published
2020

42. A transient helix in the disordered region of dynein light intermediate chain links the motor to structurally diverse adaptors for cargo transport

Author

Celestino, Ricardo, primary, Henen, Morkos A., additional, Gama, José B., additional, Carvalho, Cátia, additional, McCabe, Maxwell, additional, Barbosa, Daniel J., additional, Born, Alexandra, additional, Nichols, Parker J., additional, Carvalho, Ana X., additional, Gassmann, Reto, additional, and Vögeli, Beat, additional

Published
2019
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46. Affinity Purification of Protein Complexes in C. elegans

Author

Massachusetts Institute of Technology. Department of Biology, Whitehead Institute for Biomedical Research, Cheeseman, Iain M, Zanin, Esther, Dumont, Julien, Gassmann, Reto, Maddox, Paul, Bahmanyar, Shirin, Carvalho, Ana, Niessen, Sherry, Oegema, Karen, Desai, Arshad, Yates, John R., III, Massachusetts Institute of Technology. Department of Biology, Whitehead Institute for Biomedical Research, Cheeseman, Iain M, Zanin, Esther, Dumont, Julien, Gassmann, Reto, Maddox, Paul, Bahmanyar, Shirin, Carvalho, Ana, Niessen, Sherry, Oegema, Karen, Desai, Arshad, and Yates, John R., III

Abstract

C. elegans is a powerful metazoan model system to address fundamental questions in cell and developmental biology. Research in C. elegans has traditionally focused on genetic, physiological, and cell biological approaches. However, C. elegans is also a facile system for biochemistry: worms are easy to grow in large quantities, the functionality of tagged fusion proteins can be assessed using mutants or RNAi, and the relevance of putative interaction partners can be rapidly tested in vivo. Combining biochemistry with function-based genetic and RNA interference screens can rapidly accelerate the delineation of protein networks and pathways in diverse contexts. In this chapter, we focus on two strategies to identify protein-protein interactions: single-step immunoprecipitation and tandem affinity purification. We describe methods for growth of worms in large-scale liquid culture, preparation of worm and embryo extracts, immunoprecipitation, and tandem affinity purification. In addition, we describe methods to test specificity of antibodies, strategies for optimizing starting material, and approaches to distinguish specific from non-specific interactions. Keywords: Affinity; Culture; Epitope; Immunoblotting; Immunoprecipitation; Polyclonal

Published
2018

50. Molecular mechanism of dynein recruitment to kinetochores by the Rod–Zw10–Zwilch complex and Spindly

Author

Gama, José B., primary, Pereira, Cláudia, additional, Simões, Patrícia A., additional, Celestino, Ricardo, additional, Reis, Rita M., additional, Barbosa, Daniel J., additional, Pires, Helena R., additional, Carvalho, Cátia, additional, Amorim, João, additional, Carvalho, Ana X., additional, Cheerambathur, Dhanya K., additional, and Gassmann, Reto, additional

Published
2017
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