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An FTS/Hook/p107 FHIP Complex Interacts with and Promotes Endosomal Clustering by the Homotypic Vacuolar Protein Sorting Complex

Fused Toes (FTS) is a member of a small group of inactive variant E2 ubiquitin-conjugating enzyme domain-containing proteins of unknown function. Through proteomic analysis of FTS complexes purified from human embryonic kidney 293T cells, we identified a new multiprotein complex, the FHF complex, co...

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Bibliographic Details
Published in:Molecular biology of the cell 2008-12, Vol.19 (12), p.5059-5071
Main Authors: Xu, Lai, Sowa, Mathew E., Chen, Jing, Li, Xue, Gygi, Steven P., Harper, J. Wade
Format: Article
Language:English
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Summary:Fused Toes (FTS) is a member of a small group of inactive variant E2 ubiquitin-conjugating enzyme domain-containing proteins of unknown function. Through proteomic analysis of FTS complexes purified from human embryonic kidney 293T cells, we identified a new multiprotein complex, the FHF complex, containing FTS, members of the microtubule-binding Hook family of coiled-coil proteins (Hook1, Hook2, and Hook3), and a previously uncharacterized 107-kDa protein, FTS and Hook Interacting Protein (FHIP). FTS associated with a conserved C-terminal motif in Hook proteins in the yeast two-hybrid system and in tissue culture cells, and Hook proteins were found to form homo- and heterodimers. The ∼500-kDa FHF complex contained all three Hook proteins, and small interfering RNA depletion experiments suggest that Hook proteins can interact interchangeably within this complex. Hook proteins as well as FTS interact with members of both the class B and class C components of the homotypic vesicular protein sorting (HOPS) complex. Depletion of FTS by RNA interference affects both the trafficking of epidermal growth factor from early-to-late endosome/lysosomes and the efficiency by which overexpression of the HOPS component Vps18 promotes clustering of lysosomal-associated membrane protein 1-positive endosome/lysosomes. These data suggest that the FTS/Hook/FHIP complex functions to promote vesicle trafficking and/or fusion via the HOPS complex.
ISSN:1059-1524
1939-4586
DOI:10.1091/mbc.e08-05-0473