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

Author:

Gulluni Federico1ORCID,Prever Lorenzo1ORCID,Li Huayi1,Krafcikova Petra2ORCID,Corrado Ilaria1ORCID,Lo Wen-Ting3ORCID,Margaria Jean Piero1ORCID,Chen Anlu4,De Santis Maria Chiara1ORCID,Cnudde Sophie J.1ORCID,Fogerty Joseph5,Yuan Alex5ORCID,Massarotti Alberto6ORCID,Sarijalo Nasrin Torabi7,Vadas Oscar89ORCID,Williams Roger L.10ORCID,Thelen Marcus11ORCID,Powell David R.12ORCID,Schueler Markus13,Wiesener Michael S.7,Balla Tamas14,Baris Hagit N.151617ORCID,Tiosano Dov1517,McDermott Brian M.1819,Perkins Brian D.5ORCID,Ghigo Alessandra1ORCID,Martini Miriam1ORCID,Haucke Volker319ORCID,Boura Evzen2ORCID,Merlo Giorgio Roberto1,Buchner David A.420ORCID,Hirsch Emilio1ORCID

Affiliation:

1. Department of Molecular Biotechnology and Health Sciences, University of Turin, Turin 10126, Italy.

2. Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences, Praha, Czech Republic.

3. Leibniz-Forschungsinstitut für Molekulare Pharmakologie (FMP), 13125 Berlin, Germany.

4. Department of Biochemistry, Case Western Reserve University, Cleveland, OH 44106, USA.

5. Department of Ophthalmic Research, Cole Eye Institute, Cleveland Clinic, Cleveland, OH 44106, USA.

6. Dipartimento di Scienze del Farmaco, Università degli Studi del Piemonte Orientale, “A. Avogadro”, Largo Donegani 2, 28100 Novara, Italy.

7. Department of Nephrology and Hypertension, Friedrich-Alexander University Erlangen Nürnberg, Erlangen, Germany.

8. Section des Sciences Pharmaceutiques, University of Geneva, 1211 Geneva, Switzerland.

9. Department of Microbiology and Molecular Medicine, University of Geneva, 1211 Geneva, Switzerland.

10. Medical Research Council (MRC) Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge Biomedical Campus, Cambridge CB2 0QH, UK.

11. Institute for Research in Biomedicine, Università della Svizzera Italiana, Bellinzona, Switzerland.

12. Pharmaceutical Biology, Lexicon Pharmaceuticals, The Woodlands, TX 77381, USA.

13. Division of Nephrology and Internal Intensive Care Medicine, Charite University, Berlin, Germany.

14. Section on Molecular Signal Transduction, Program for Developmental Neuroscience, Eunice Kennedy Shriver NICHD, National Institutes of Health, Bethesda, MD 20892, USA.

15. Division of Pediatric Endocrinology, Ruth Children’s Hospital, Rambam Medical Center, Haifa 30196, Israel.

16. The Genetics Institute, Rambam Health Care Campus, Haifa, Israel.

17. Rappaport Family Faculty of Medicine, Technion–Israel Institute of Technology, Haifa 30196, Israel.

18. Department of Otolaryngology–Head and Neck Surgery, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA.

19. Freie Universität Berlin, Faculty of Biology, Chemistry and Pharmacy, 14195 Berlin, Germany.

20. Department of Genetics and Genome Sciences, Case Western Reserve University, Cleveland, OH 44106, USA.

Abstract

ESCRTing lenses away from senescence ESCRT proteins control membrane fusion in various key cellular processes, but the mechanisms involved are still incompletely understood. Gulluni et al . report that ESCRT recruitment at the cytokinetic bridge is mediated by the binding of an ESCRT-II subunit to the signaling lipid phosphatidylinositol 3,4-bisphosphate (see the Perspective by Brill and Wilde). This pathway acts in parallel to a known cascade driven by a protein called ALIX, but its failure is sufficient to lead to premature senescence in the lens of fish, mouse, and human eyes, where ALIX is expressed at lower levels. These results point to an evolutionarily conserved pathway for the cell-specific control of cytokinesis that serves to protect from senescence and the early onset of cataracts. —SMH

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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