PI(3,4)P2-mediated cytokinetic abscission prevents early senescence and cataract formation
| Autor: | Federico Gulluni, Lorenzo Prever, Huayi Li, Petra Krafcikova, Ilaria Corrado, Wen-Ting Lo, Jean Piero Margaria, Anlu Chen, Maria Chiara De Santis, Sophie J. Cnudde, Joseph Fogerty, Alex Yuan, Alberto Massarotti, Nasrin Torabi Sarijalo, Oscar Vadas, Roger L. Williams, Marcus Thelen, David R. Powell, Markus Schueler, Michael S. Wiesener, Tamas Balla, Hagit N. Baris, Dov Tiosano, Brian M. McDermott, Brian D. Perkins, Alessandra Ghigo, Miriam Martini, Volker Haucke, Evzen Boura, Giorgio Roberto Merlo, David A. Buchner, Emilio Hirsch |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Phosphatidylinositol 4
5-Diphosphate Multidisciplinary Endosomal Sorting Complexes Required for Transport Calcium-Binding Proteins Aging Premature Cell Cycle Proteins macromolecular substances Zebrafish Proteins Phosphatidylinositols Biological Evolution Lipids Cataract Article Cell Line Mice Phosphatidylinositol 3-Kinases Tubulin Lens Crystalline Mutation Animals Humans Cellular Senescence Zebrafish Cytokinesis |
| Zdroj: | Science |
| Popis: | 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 phosphatidylinositol-4-phosphate 3-kinase catalytic subunit type 2α (PI3K-C2α), its lipid product PI(3,4)P2 (phosphatidylinositol 3,4-bisphosphate), and the PI(3,4)P2-–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. |
| Databáze: | OpenAIRE |
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