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

Federico Gulluni; Lorenzo Prever; Huayi Li; Petra Krafcikova; Ilaria Corrado; Wen Ting Lo; Jean Piero Margaria; Anlu Chen; Maria Chiara de Santis; Sophie J. Cnudde; Joseph Fogerty; Alex Yuan; Alberto Massarotti; Nasrin Torabi Sarijalo; Oscar Vadas; Roger L. Williams; Marcus Thelen; David R. Powell; Markus Schueler; Michael S. Wiesener; Tamas Balla; Hagit N. Baris; Dov Tiosano; Brian M. McDermott; Brian D. Perkins; Alessandra Ghigo; Miriam Martini; Volker Haucke; Evzen Boura; Giorgio Roberto Merlo; David A. Buchner; Emilio Hirsch

doi:10.1126/science.abk0410

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

Federico Gulluni, Lorenzo Prever, Huayi Li, Petra Krafcikova, Ilaria Corrado, Wen Ting Lo, Jean Piero Margaria, Anlu Chen, Maria Chiara de Santis, Sophie J. Cnudde, Joseph Fogerty, Alex Yuan, Alberto Massarotti, Nasrin Torabi Sarijalo, Oscar Vadas, Roger L. Williams, Marcus Thelen, David R. Powell, Markus Schueler, Michael S. WiesenerTamas Balla, Hagit N. Baris, Dov Tiosano, Brian M. McDermott, Brian D. Perkins, Alessandra Ghigo, Miriam Martini, Volker Haucke, Evzen Boura, Giorgio Roberto Merlo, David A. Buchner, Emilio Hirsch

Dipartimento di Scienze del Farmaco

Risultato della ricerca: Contributo su rivista › Articolo in rivista › peer review

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.

Lingua originale	Inglese
Numero di articolo	1339
Rivista	Science
Volume	374
Numero di pubblicazione	6573
DOI	https://doi.org/10.1126/science.abk0410
Stato di pubblicazione	Pubblicato - 10 dic 2021

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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., ... Hirsch, E. (2021). PI(3,4)P2-mediated cytokinetic abscission prevents early senescence and cataract formation. Science, 374(6573), Articolo 1339. https://doi.org/10.1126/science.abk0410

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

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.",

author = "Federico Gulluni and Lorenzo Prever and Huayi Li and Petra Krafcikova and Ilaria Corrado and Lo, {Wen Ting} and Margaria, {Jean Piero} and Anlu Chen and {de Santis}, {Maria Chiara} and Cnudde, {Sophie J.} and Joseph Fogerty and Alex Yuan and Alberto Massarotti and Sarijalo, {Nasrin Torabi} and Oscar Vadas and Williams, {Roger L.} and Marcus Thelen and Powell, {David R.} and Markus Schueler and Wiesener, {Michael S.} and Tamas Balla and Baris, {Hagit N.} and Dov Tiosano and McDermott, {Brian M.} and Perkins, {Brian D.} and Alessandra Ghigo and Miriam Martini and Volker Haucke and Evzen Boura and Merlo, {Giorgio Roberto} and Buchner, {David A.} and Emilio Hirsch",

year = "2021",

month = dec,

day = "10",

doi = "10.1126/science.abk0410",

language = "English",

volume = "374",

journal = "Science",

issn = "0036-8075",

publisher = "American Association for the Advancement of Science",

number = "6573",

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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, Sarijalo, NT, Vadas, O, Williams, RL, Thelen, M, Powell, DR, Schueler, M, Wiesener, MS, 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, 'PI(3,4)P2-mediated cytokinetic abscission prevents early senescence and cataract formation', Science, vol. 374, n. 6573, 1339. https://doi.org/10.1126/science.abk0410

TY - JOUR

T1 - PI(3,4)P2-mediated cytokinetic abscission prevents early senescence and cataract formation

AU - Gulluni, Federico

AU - Prever, Lorenzo

AU - Li, Huayi

AU - Krafcikova, Petra

AU - Corrado, Ilaria

AU - Lo, Wen Ting

AU - Margaria, Jean Piero

AU - Chen, Anlu

AU - de Santis, Maria Chiara

AU - Cnudde, Sophie J.

AU - Fogerty, Joseph

AU - Yuan, Alex

AU - Massarotti, Alberto

AU - Sarijalo, Nasrin Torabi

AU - Vadas, Oscar

AU - Williams, Roger L.

AU - Thelen, Marcus

AU - Powell, David R.

AU - Schueler, Markus

AU - Wiesener, Michael S.

AU - Balla, Tamas

AU - Baris, Hagit N.

AU - Tiosano, Dov

AU - McDermott, Brian M.

AU - Perkins, Brian D.

AU - Ghigo, Alessandra

AU - Martini, Miriam

AU - Haucke, Volker

AU - Boura, Evzen

AU - Merlo, Giorgio Roberto

AU - Buchner, David A.

AU - Hirsch, Emilio

PY - 2021/12/10

Y1 - 2021/12/10

N2 - 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.

AB - 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.

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U2 - 10.1126/science.abk0410

DO - 10.1126/science.abk0410

M3 - Article

SN - 0036-8075

VL - 374

JO - Science

JF - Science

IS - 6573

M1 - 1339

ER -

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

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