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Biochemical analyses of human IST1 and its function in cytokinesis.

Authors
  • Bajorek, Monika
  • Morita, Eiji
  • Skalicky, Jack J
  • Morham, Scott G
  • Babst, Markus
  • Sundquist, Wesley I
Type
Published Article
Journal
Molecular Biology of the Cell
Publisher
American Society for Cell Biology
Publication Date
Mar 01, 2009
Volume
20
Issue
5
Pages
1360–1373
Identifiers
DOI: 10.1091/mbc.E08-05-0475
PMID: 19129479
Source
Medline
License
Unknown

Abstract

The newly described yeast endosomal sorting complexes required for transport (ESCRT) protein increased sodium tolerance-1 (Ist1p) binds the late-acting ESCRT proteins Did2p/charged MVB protein (CHMP) 1 and Vps4p and exhibits synthetic vacuolar protein sorting defects when combined with mutations in the Vta1p/LIP5-Vps60p/CHMP5 complex. Here, we report that human IST1 also functions in the ESCRT pathway and is required for efficient abscission during HeLa cell cytokinesis. IST1 binding interactions with VPS4, CHMP1, LIP5, and ESCRT-I were characterized, and the IST1-VPS4 interaction was investigated in detail. Mutational and NMR spectroscopic studies revealed that the IST1 terminus contains two distinct MIT interacting motifs (MIM1 and MIM2) that wrap around and bind in different groves of the MIT helical bundle. IST1, CHMP1, and VPS4 were recruited to the midbodies of dividing cells, and depleting either IST1 or CHMP1 proteins blocked VPS4 recruitment and abscission. In contrast, IST1 depletion did not inhibit human immunodeficiency virus-1 budding. Thus, IST1 and CHMP1 act together to recruit and modulate specific VPS4 activities required during the final stages of cell division.

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