title: An FTS/Hook/p107(FHIP) complex interacts with and promotes endosomal clustering by the homotypic vacuolar protein sorting complex.
abstract: 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 approximately 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.
authors.affiliation: Department of Pathology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Lai
authors.initials: L
authors.lastname: Xu
authors.forename: Mathew E
authors.initials: ME
authors.lastname: Sowa
authors.forename: Jing
authors.initials: J
authors.lastname: Chen
authors.forename: Xue
authors.initials: X
authors.lastname: Li
authors.forename: Steven P
authors.initials: SP
authors.lastname: Gygi
authors.forename: J Wade
authors.initials: JW
authors.lastname: Harper
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D011992:Endosomes / Q000378:metabolism*; D006801:Humans; D008247:Lysosomes / Q000378:metabolism; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D046912:Multiprotein Complexes / Q000378:metabolism*; D011487:Protein Conformation; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D021381:Protein Transport; D034622:RNA Interference; D050720:Retinoblastoma-Like Protein p107 / Q000235:genetics / Q000378:metabolism*; D016415:Sequence Alignment; D044763:Ubiquitin-Conjugating Enzymes / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D014617:Vacuoles / Q000378:metabolism*
chemical_list: C486377:AKTIP protein, human; D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; D008869:Microtubule-Associated Proteins; D046912:Multiprotein Complexes; D020033:Protein Isoforms; D050720:Retinoblastoma-Like Protein p107; C471055:hook1 protein, human; C097308:UBE2D1 protein, human; D044763:Ubiquitin-Conjugating Enzymes
references.citation: J Cell Sci. 2002 Jul 1;115(Pt 13):2627-37
references.pmid: 12077354
references.citation: Mol Cell Biol. 2004 Feb;24(4):1493-504
references.pmid: 14749367
references.citation: Nature. 2003 Sep 18;425(6955):316-21
references.pmid: 13679922
references.citation: Annu Rev Biophys Biomol Struct. 2007;36:131-50
references.pmid: 17477837
references.citation: J Biol Chem. 2001 Aug 3;276(31):29393-402
references.pmid: 11382755
references.citation: Cell. 2007 May 4;129(3):485-98
references.pmid: 17442384
references.citation: Mol Cell. 1999 Oct;4(4):479-86
references.pmid: 10549280
references.citation: Mol Biol Cell. 2003 Oct;14(10):4015-27
references.pmid: 14517315
references.citation: Biochim Biophys Acta. 2004 Nov 29;1695(1-3):55-72
references.pmid: 15571809
references.citation: Mol Cell. 2006 Sep 1;23(5):709-21
references.pmid: 16949367
references.citation: J Cell Biol. 2004 Oct 25;167(2):281-92
references.pmid: 15504911
references.citation: Nat Struct Biol. 2001 Aug;8(8):650-2
references.pmid: 11473244
references.citation: Genetics. 1999 Feb;151(2):675-84
references.pmid: 9927460
references.citation: Cell. 2003 Dec 26;115(7):825-36
references.pmid: 14697201
references.citation: Curr Opin Cell Biol. 1999 Aug;11(4):453-9
references.pmid: 10449330
references.citation: J Cell Biol. 2000 Sep 4;150(5):F111-6
references.pmid: 10974009
references.citation: Nature. 1994 Sep 1;371(6492):80-3
references.pmid: 8072533
references.citation: Cell. 2001 Jul 27;106(2):145-55
references.pmid: 11511343
references.citation: Science. 1993 Nov 26;262(5138):1401-7
references.pmid: 8248779
references.citation: J Mol Biol. 2007 Mar 16;367(1):204-11
references.pmid: 17240395
references.citation: Mol Cell. 2006 Mar 17;21(6):873-80
references.pmid: 16543155
references.citation: Traffic. 2007 Jan;8(1):32-46
references.pmid: 17140400
references.citation: Mamm Genome. 1997 Dec;8(12):879-83
references.pmid: 9383278
references.citation: Mol Biol Cell. 2000 Sep;11(9):3137-53
references.pmid: 10982406
references.citation: Mol Biol Cell. 2004 Mar;15(3):1197-210
references.pmid: 14668490
references.citation: Mol Cell. 2004 Mar 26;13(6):783-9
references.pmid: 15053872
references.citation: J Cell Biol. 2001 Mar 5;152(5):923-34
references.pmid: 11238449
references.citation: Annu Rev Biophys Biomol Struct. 2006;35:277-98
references.pmid: 16689637
references.citation: J Cell Biol. 2002 Apr 1;157(1):91-101
references.pmid: 11916981
references.citation: Structure. 2004 Sep;12(9):1563-74
references.pmid: 15341722
references.citation: J Cell Biol. 2001 Jul 9;154(1):109-22
references.pmid: 11448994
references.citation: J Cell Biol. 1996 Jun;133(6):1205-15
references.pmid: 8682859
references.citation: Trends Cell Biol. 1998 Jul;8(7):257-9
references.pmid: 9714595
references.citation: Cell. 2006 Apr 7;125(1):113-26
references.pmid: 16615894
references.citation: Mol Biol Cell. 1999 Apr;10(4):847-59
references.pmid: 10198042
references.citation: Nat Struct Mol Biol. 2006 Oct;13(10):915-20
references.pmid: 16980971