PI(3,4)P2-mediated cytokinetic abscission prevents early senescence and cataract formation.
Gulluni Federico,Prever Lorenzo,Li Huayi,Krafcikova Petra,Corrado Ilaria,Lo Wen-Ting,Margaria Jean Piero,Chen Anlu,De Santis Maria Chiara,Cnudde Sophie J,Fogerty Joseph,Yuan Alex,Massarotti Alberto,Sarijalo Nasrin Torabi,Vadas Oscar,Williams Roger L,Thelen Marcus,Powell David R,Schueler Markus,Wiesener Michael S,Balla Tamas,Baris Hagit N,Tiosano Dov,McDermott Brian M,Perkins Brian D,Ghigo Alessandra,Martini Miriam,Haucke Volker,Boura Evzen,Merlo Giorgio Roberto,Buchner David A,Hirsch Emilio
Science (New York, N.Y.)
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-C2α (phosphatidylinositol-4-phosphate 3-kinase catalytic subunit type 2α), its lipid product PI(3,4)P (phosphatidylinositol 3,4-bisphosphate), and the PI(3,4)P–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.