PI(3,4)P2-mediated cytokinetic abscission prevents early senescence and cataract formation

0550775 - ÚOCHB 2022 RIV US eng J - Journal Article
Gulluni, F. - Prever, L. - Li, H. - Krafčíková, Petra - Corrado, I. - Lo, W.-T. - Margaria, J. P. - Chen, A. - De Santis, M. C. - Cnudde, S. J. - Fogerty, J. - Yuan, A. - Massarotti, A. - Sarijalo, N. T. - Vadas, O. - Williams, R. L. - Thelen, M. - Powell, D. R. - Schueler, M. - Wiesener, M. S. - Balla, T. - Baris, H. N. - Tiosano, D. - McDermott, B. M. - Perkins, B. D. - Ghigo, A. - Martini, M. - Haucke, V. - Bouřa, Evžen - Merlo, G. R. - Buchner, D. A. - Hirsch, E.
PI(3,4)P2-mediated cytokinetic abscission prevents early senescence and cataract formation.
Science. Roč. 374, č. 6573 (2021), č. článku eabk0410. ISSN 0036-8075. E-ISSN 1095-9203
Institutional support: RVO:61388963
Keywords : escrt-iii * ubiquitin recognition * molecular-mechanisms
OECD category: Biochemistry and molecular biology
Impact factor: 63.832, year: 2021
Method of publishing: Limited access
https://doi.org/10.1126/science.abk0410

Cytokinetic membrane abscission is a spatially and temporally regulated process that requires ESCRT (endosomal sorting complexes required for transport)-dependent control of membrane remodeling at the midbody, a subcellular organelle that defines the cleavage site. Alteration of ESCRT function can lead to cataract, but the underlying mechanism and its relation to cytokinesis are unclear. We found a lens-specific cytokinetic process that required PI3K-C2 alpha (phosphatidylinositol-4-phosphate 3-kinase catalytic subunit type 2 alpha), its lipid product PI(3,4)P-2 (phosphatidylinositol 3,4-bisphosphate), and the PI(3,4)P-2-binding ESCRT-II subunit VPS36 (vacuolar protein-sorting-associated protein 36). Loss of each of these components led to impaired cytokinesis, triggering premature senescence in the lens of fish, mice, and humans. Thus, an evolutionarily conserved pathway underlies the cell type-specific control of cytokinesis that helps to prevent early onset cataract by protecting from senescence.
Permanent Link: http://hdl.handle.net/11104/0326084