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)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.

Department of Biochemistry Case Western Reserve University Cleveland OH 44106 USA

Department of Genetics and Genome Sciences Case Western Reserve University Cleveland OH 44106 USA

Department of Microbiology and Molecular Medicine University of Geneva 1211 Geneva Switzerland

Department of Molecular Biotechnology and Health Sciences University of Turin Turin 10126 Italy

Department of Nephrology and Hypertension Friedrich Alexander University Erlangen Nürnberg Erlangen Germany

Department of Ophthalmic Research Cole Eye Institute Cleveland Clinic Cleveland OH 44106 USA

Department of Otolaryngology Head and Neck Surgery Case Western Reserve University School of Medicine Cleveland OH 44106 USA

Dipartimento di Scienze del Farmaco Università degli Studi del Piemonte Orientale A Avogadro Largo Donegani 2 28100 Novara Italy

Division of Nephrology and Internal Intensive Care Medicine Charite University Berlin Germany

Division of Pediatric Endocrinology Ruth Children's Hospital Rambam Medical Center Haifa 30196 Israel

Freie Universität Berlin Faculty of Biology Chemistry and Pharmacy 14195 Berlin Germany

Institute for Research in Biomedicine Università della Svizzera Italiana Bellinzona Switzerland

Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences Praha Czech Republic

Leibniz Forschungsinstitut für Molekulare Pharmakologie 13125 Berlin Germany

Medical Research Council Laboratory of Molecular Biology Francis Crick Avenue Cambridge Biomedical Campus Cambridge CB2 0QH UK

Pharmaceutical Biology Lexicon Pharmaceuticals The Woodlands TX 77381 USA

Rappaport Family Faculty of Medicine Technion Israel Institute of Technology Haifa 30196 Israel

Section des Sciences Pharmaceutiques University of Geneva 1211 Geneva Switzerland

Section on Molecular Signal Transduction Program for Developmental Neuroscience Eunice Kennedy Shriver NICHD National Institutes of Health Bethesda MD 20892 USA

The Genetics Institute Rambam Health Care Campus Haifa Israel

Comment In

Science. 2021 Dec 10;374(6573):1318-1319. doi: 10.1126/science.abm7949. PubMed

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