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Selective autophagy maintains centrosome integrity and accurate mitosis by turnover of centriolar satellites
- Source :
- Nature Communications, Vol 10, Iss 1, Pp 1-19 (2019), Holdgaard, S G, Cianfanelli, V, Pupo, E, Lambrughi, M, Lubas, M, Nielsen, J C, Eibes, S, Maiani, E, Harder, L M, Wesch, N, Foged, M M, Maeda, K, Nazio, F, de la Ballina, L R, Dötsch, V, Brech, A, Frankel, L B, Jäättelä, M, Locatelli, F, Barisic, M, Andersen, J S, Bekker-Jensen, S, Lund, A H, Rogov, V V, Papaleo, E, Lanzetti, L, De Zio, D & Cecconi, F 2019, ' Selective autophagy maintains centrosome integrity and accurate mitosis by turnover of centriolar satellites ', Nature Communications, vol. 10, 4176, pp. 4176 . https://doi.org/10.1038/s41467-019-12094-9, Holdgaard, S G, Cianfanelli, V, Pupo, E, Lambrughi, M, Lubas, M, Nielsen, J C, Eibes, S, Maiani, E, Harder, L M, Wesch, N, Foged, M M, Maeda, K, Nazio, F, de la Ballina, L R, Dötsch, V, Brech, A, Frankel, L B, Jäättelä, M, Locatelli, F, Barisic, M, Andersen, J S, Bekker-Jensen, S, Lund, A H, Rogov, V V, Papaleo, E, Lanzetti, L, De Zio, D & Cecconi, F 2019, ' Selective autophagy maintains centrosome integrity and accurate mitosis by turnover of centriolar satellites ', Nature Communications, vol. 10, no. 1, 4176, pp. 1-19 . https://doi.org/10.1038/s41467-019-12094-9, Nature Communications
- Publication Year :
- 2019
-
Abstract
- The centrosome is the master orchestrator of mitotic spindle formation and chromosome segregation in animal cells. Centrosome abnormalities are frequently observed in cancer, but little is known of their origin and about pathways affecting centrosome homeostasis. Here we show that autophagy preserves centrosome organization and stability through selective turnover of centriolar satellite components, a process we termed doryphagy. Autophagy targets the satellite organizer PCM1 by interacting with GABARAPs via a C-terminal LIR motif. Accordingly, autophagy deficiency results in accumulation of large abnormal centriolar satellites and a resultant dysregulation of centrosome composition. These alterations have critical impact on centrosome stability and lead to mitotic centrosome fragmentation and unbalanced chromosome segregation. Our findings identify doryphagy as an important centrosome-regulating pathway and bring mechanistic insights to the link between autophagy dysfunction and chromosomal instability. In addition, we highlight the vital role of centriolar satellites in maintaining centrosome integrity.<br />Centrosomes drive mitotic spindle formation and chromosome segregation. Here, the authors show that centrosome stability is regulated by selective autophagic degradation of centriolar satellite components in a process they term doryphagy, connecting autophagy and chromosomal integrity.
- Subjects :
- 0301 basic medicine
Magnetic Resonance Spectroscopy
Settore BIO/06
Centriole
Science
Immunoblotting
General Physics and Astronomy
Mitosis
Biology
Molecular Dynamics Simulation
Microtubules
General Biochemistry, Genetics and Molecular Biology
Article
Mass Spectrometry
Fluorescence
Cell Line
Chromosome segregation
03 medical and health sciences
0302 clinical medicine
PCM1
Microtubule
Cell Line, Tumor
Macroautophagy
Autophagy
Humans
microtubule nucleation
protein
localization
gabarap
multipolarity
organization
components
database
binding
cep131
lcsh:Science
Centrioles
Centrosome
Chromatography
Liquid
Microscopy
Multidisciplinary
Tumor
Cell Cycle
General Chemistry
Cell biology
030104 developmental biology
Chromatography, Liquid
Microscopy, Fluorescence
Settore MED/38 - PEDIATRIA GENERALE E SPECIALISTICA
030220 oncology & carcinogenesis
lcsh:Q
Centriolar satellite
Subjects
Details
- Language :
- English
- ISSN :
- 20411723
- Database :
- OpenAIRE
- Journal :
- Nature Communications, Vol 10, Iss 1, Pp 1-19 (2019), Holdgaard, S G, Cianfanelli, V, Pupo, E, Lambrughi, M, Lubas, M, Nielsen, J C, Eibes, S, Maiani, E, Harder, L M, Wesch, N, Foged, M M, Maeda, K, Nazio, F, de la Ballina, L R, Dötsch, V, Brech, A, Frankel, L B, Jäättelä, M, Locatelli, F, Barisic, M, Andersen, J S, Bekker-Jensen, S, Lund, A H, Rogov, V V, Papaleo, E, Lanzetti, L, De Zio, D & Cecconi, F 2019, ' Selective autophagy maintains centrosome integrity and accurate mitosis by turnover of centriolar satellites ', Nature Communications, vol. 10, 4176, pp. 4176 . https://doi.org/10.1038/s41467-019-12094-9, Holdgaard, S G, Cianfanelli, V, Pupo, E, Lambrughi, M, Lubas, M, Nielsen, J C, Eibes, S, Maiani, E, Harder, L M, Wesch, N, Foged, M M, Maeda, K, Nazio, F, de la Ballina, L R, Dötsch, V, Brech, A, Frankel, L B, Jäättelä, M, Locatelli, F, Barisic, M, Andersen, J S, Bekker-Jensen, S, Lund, A H, Rogov, V V, Papaleo, E, Lanzetti, L, De Zio, D & Cecconi, F 2019, ' Selective autophagy maintains centrosome integrity and accurate mitosis by turnover of centriolar satellites ', Nature Communications, vol. 10, no. 1, 4176, pp. 1-19 . https://doi.org/10.1038/s41467-019-12094-9, Nature Communications
- Accession number :
- edsair.doi.dedup.....d20da61559cd0c0cf8e5f0e33705d0ff
- Full Text :
- https://doi.org/10.1038/s41467-019-12094-9