Differential requirements for Alix and ESCRT-III in cytokinesis and HIV-1 release
- Department of Infectious Diseases, King's College London School of Medicine, London SE1 9RT, United Kingdom
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Edited by Robert A. Lamb, Northwestern University, Evanston, IL, and approved April 23, 2008 (received for review February 28, 2008)
Abstract
The ESCRT machinery functions in topologically equivalent membrane fission events, namely multivesicular body formation, the terminal stages of cytokinesis and HIV-1 release. Here, we show that the ESCRT-III-binding protein Alix is recruited to the midbody of dividing cells through binding Cep55 via an evolutionarily conserved peptide. Disruption of Cep55/Alix/ESCRT-III interactions causes formation of aberrant midbodies and cytokinetic failure, demonstrating an essential role for these proteins in midbody morphology and cell division. We also show that the C terminus of Alix encodes a multimerization activity that is essential for its function in Alix-dependent HIV-1 release and for interaction with Tsg101. Last, we demonstrate that overexpression of Chmp4b and Chmp4c differentially inhibits HIV-1 release and cytokinesis, suggesting possible reasons for gene expansion within the mammalian Class E VPS pathway.
Footnotes
- *To whom correspondence should be addressed. E-mail: juan.martin_serrano{at}kcl.ac.uk
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Author contributions: J.G.C., M.A., and J.M.-S. designed research; J.G.C. and M.A. performed research; J.G.C., M.A., and J.M.-S. analyzed data; and J.G.C. and J.M.-S. wrote the paper.
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The authors declare no conflict of interest.
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This article is a PNAS Direct Submission.
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This article contains supporting information online at www.pnas.org/cgi/content/full/0802008105/DCSupplemental.
- © 2008 by The National Academy of Sciences of the USA
