Differential requirements for Alix and ESCRT-III in cytokinesis and HIV-1 release
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.
- Publication:
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Proceedings of the National Academy of Science
- Pub Date:
- July 2008
- DOI:
- 10.1073/pnas.0802008105
- Bibcode:
- 2008PNAS..10510541C
- Keywords:
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- Biological Sciences:Medical Sciences