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

Gulluni F, Prever L, Li H, Krafcikova P, Corrado I, Lo WT, Margaria JP, Chen A, De Santis MC, Cnudde SJ, Fogerty J, Yuan A, Massarotti A, Torabi Sarijalo N, Vadas O, Williams RL, Thelen M, Powell DR, Schueler M, Wiesener M, Balla T, Baris HN, Tiosano D, Mcdermott BM, Perkins BD, Ghigo A, Martini M, Haucke V, Boura E, Merlo GR, Buchner DA, Hirsch E (2021)

Publication Type: Journal article

Publication year: 2021

Journal

Science American Association for the Advancement of Science

Book Volume: 374

Article Number: 1339

Journal Issue: 6573

DOI: 10.1126/science.abk0410

Abstract

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-C2a (phosphatidylinositol-4-phosphate 3-kinase catalytic subunit type 2a), 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.

Authors with CRIS profile

Nasrin Torabi Sarijalo FAU Optical Imaging Competence Center (FAU OICE) Michael Wiesener Professur für Innere Medizin (Nephrologie)

Involved external institutions

Cleveland Clinic US United States (USA) (US) University of Turin / Università degli Studi di Torino (UNITO) IT Italy (IT) University of Geneva / Université de Genève (UNIGE) CH Switzerland (CH) Case Western Reserve University US United States (USA) (US) Università della Svizzera italiana (USI) CH Switzerland (CH) Academy of Sciences of the Czech Republic (ASCR) / Akademie věd České republiky (AVČR) CZ Czech Republic (CZ) Lexicon Pharmaceuticals, Inc. US United States (USA) (US) University of Eastern Piedmont / Università degli Studi del Piemonte Orientale "Amedeo Avogadro" IT Italy (IT) US National Institutes of Health (NIH) US United States (USA) (US) Charité - Universitätsmedizin Berlin DE Germany (DE) MRC Laboratory of Molecular Biology DE Germany (DE) Leibniz-Forschungsinstitut für Molekulare Pharmakologie im Forschungsverbund Berlin e.V. (FMP) DE Germany (DE) Rambam Health Care Campus IL Israel (IL)

How to cite

APA:

Gulluni, F., Prever, L., Li, H., Krafcikova, P., Corrado, I., Lo, W.-T.,... Hirsch, E. (2021). PI(3,4)P2-mediated cytokinetic abscission prevents early senescence and cataract formation. Science, 374(6573). https://doi.org/10.1126/science.abk0410

MLA:

Gulluni, Federico, et al. "PI(3,4)P2-mediated cytokinetic abscission prevents early senescence and cataract formation." Science 374.6573 (2021).

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