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

• DOI: 10.1126/science.abk0410
• Publication Date: 2021-12-09T18:58:36Z
• Authors: Federico Gulluni; Lorenzo Prever; Huayi Li; Petra Krafcikova; Ilaria Corrado; Wen-Ting Lo; Jean Piero Margaria; Anlu Chen; Maria Chiara De S...; Sophie J. Cnudde; Joseph Fogerty; Alex Yuan; Alberto Massarotti; Nasrin Torabi Sar...; 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 M...; David A. Buchner; Emilio Hirsch
• Keywords: Phosphatidylinositol 4,5-Diphosphate; 570; senescence; Endosomal Sorting Complexes Required for Transport; Calcium-Binding Proteins; cytokinesis; Aging, Premature; Cell Cycle Proteins; Zebrafish Proteins; Phosphatidylinositols; PI3K; Biological Evolution; Cataract; Cell Line; Mice; Phosphatidylinositol 3-Kinases; Tubulin; Lens, Crystalline; Mutation; Animals; Humans; Cellular Senescence; Zebrafish; Cytokinesis

ESCRTing lenses away from senescence

ESCRT proteins control membrane fusion in various key cellular processes, but the mechanisms involved are still incompletely understood. Gulluni et al . report that ESCRT recruitment at the cytokinetic bridge is mediated by the binding of an ESCRT-II subunit to the signaling lipid phosphatidylinositol 3,4-bisphosphate (see the Perspective by Brill and Wilde). This pathway acts in parallel to a known cascade driven by a protein called ALIX, but its failure is sufficient to lead to premature senescence in the lens of fish, mouse, and human eyes, where ALIX is expressed at lower levels. These results point to an evolutionarily conserved pathway for the cell-specific control of cytokinesis that serves to protect from senescence and the early onset of cataracts. —SMH