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.

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

Gulluni F.;Li H.;Corrado I.;Margaria J. P.;Chen A.;de Santis M. C.;Ghigo A.;Martini M.;Merlo G. R.;Hirsch E.
2021

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.
SCIENCE
374
6573
1
14
Gulluni F.; Prever L.; Li H.; Krafcikova P.; Corrado I.; Lo W.-T.; Margaria J.P.; Chen A.; de Santis M.C.; Cnudde S.J.; Fogerty J.; Yuan A.; Massarotti A.; Sarijalo N.T.; Vadas O.; Williams R.L.; Thelen M.; Powell D.R.; Schueler M.; Wiesener M.S.; Balla T.; Baris H.N.; Tiosano D.; McDermott B.M.; Perkins B.D.; Ghigo A.; Martini M.; Haucke V.; Boura E.; Merlo G.R.; Buchner D.A.; Hirsch E.
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2318/1831621
Citazioni
  • ???jsp.display-item.citation.pmc??? 1
  • Scopus 1
  • ???jsp.display-item.citation.isi??? 3
social impact