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

Science. 2021 Dec 10;374(6573):eabk0410. doi: 10.1126/science.abk0410. Epub 2021 Dec 10.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging, Premature
  • Animals
  • Biological Evolution
  • Calcium-Binding Proteins / metabolism
  • Cataract / metabolism
  • Cataract / pathology*
  • Cell Cycle Proteins / metabolism
  • Cell Line
  • Cellular Senescence*
  • Cytokinesis*
  • Endosomal Sorting Complexes Required for Transport / metabolism*
  • Humans
  • Lens, Crystalline / cytology*
  • Lens, Crystalline / growth & development
  • Lens, Crystalline / metabolism
  • Mice
  • Mutation
  • Phosphatidylinositol 3-Kinases / genetics
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Phosphatidylinositol 4,5-Diphosphate / metabolism
  • Phosphatidylinositols / metabolism*
  • Tubulin / metabolism
  • Zebrafish
  • Zebrafish Proteins / genetics
  • Zebrafish Proteins / metabolism


  • CHMP4B protein, human
  • Calcium-Binding Proteins
  • Cell Cycle Proteins
  • Endosomal Sorting Complexes Required for Transport
  • PDCD6IP protein, human
  • Phosphatidylinositol 4,5-Diphosphate
  • Phosphatidylinositols
  • Tubulin
  • VPS36 protein, human
  • Zebrafish Proteins
  • phosphoinositide-3,4-bisphosphate
  • PIK3C2A protein, human
  • Pik3c2a protein, mouse