PUBLICATION
PI(3,4)P2-mediated cytokinetic abscission prevents early senescence and cataract formation
- Authors
- 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.
- ID
- ZDB-PUB-211224-2
- Date
- 2021
- Source
- Science (New York, N.Y.) 374: eabk0410 (Journal)
- Registered Authors
- Keywords
- none
- 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
- PubMed
- 34882480 Full text @ Science
Citation
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. (2021) PI(3,4)P2-mediated cytokinetic abscission prevents early senescence and cataract formation. Science (New York, N.Y.). 374:eabk0410.
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-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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping