title: UBAP1 is a component of an endosome-specific ESCRT-I complex that is essential for MVB sorting.
abstract: Endosomal sorting complexes required for transport (ESCRTs) regulate several events involving membrane invagination, including multivesicular body (MVB) biogenesis, viral budding, and cytokinesis. In each case, upstream ESCRTs combine with additional factors, such as Bro1 proteins, to recruit ESCRT-III and the ATPase VPS4 in order to drive membrane scission. A clue to understanding how such diverse cellular processes might be controlled independently of each other has been the identification of ESCRT isoforms. Mammalian ESCRT-I comprises TSG101, VPS28, VPS37A-D, and MVB12A/B. These could generate several ESCRT-I complexes, each targeted to a different compartment and able to recruit distinct ESCRT-III proteins. Here we identify a novel ESCRT-I component, ubiquitin-associated protein 1 (UBAP1), which contains a region conserved in MVB12. UBAP1 binds the endosomal Bro1 protein His domain protein tyrosine phosphatase (HDPTP), but not Alix, a Bro1 protein involved in cytokinesis. UBAP1 is required for sorting EGFR to the MVB and for endosomal ubiquitin homeostasis, but not for cytokinesis. UBAP1 is part of a complex that contains a fraction of total cellular TSG101 and that also contains VPS37A but not VPS37C. Hence, the presence of UBAP1, in combination with VPS37A, defines an endosome-specific ESCRT-I complex.
authors.affiliation: Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, UK.
authors.forename: Flavia
authors.initials: F
authors.lastname: Stefani
authors.forename: Ling
authors.initials: L
authors.lastname: Zhang
authors.forename: Sandra
authors.initials: S
authors.lastname: Taylor
authors.forename: Johanna
authors.initials: J
authors.lastname: Donovan
authors.forename: Sara
authors.initials: S
authors.lastname: Rollinson
authors.forename: Aurelie
authors.initials: A
authors.lastname: Doyotte
authors.forename: Kim
authors.initials: K
authors.lastname: Brownhill
authors.forename: Janis
authors.initials: J
authors.lastname: Bennion
authors.forename: Stuart
authors.initials: S
authors.lastname: Pickering-Brown
authors.forename: Philip
authors.initials: P
authors.lastname: Woodman
mesh_terms: D000251:Adenosine Triphosphatases / Q000378:metabolism; D048749:Cytokinesis; D056827:Endosomal Sorting Complexes Required for Transport / Q000737:chemistry / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D046912:Multiprotein Complexes / Q000378:metabolism; D057146:Multivesicular Bodies / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000378:metabolism; D025801:Ubiquitin / Q000378:metabolism
chemical_list: C480237:Bro1 protein, S cerevisiae; D056827:Endosomal Sorting Complexes Required for Transport; D046912:Multiprotein Complexes; D029701:Saccharomyces cerevisiae Proteins; D025801:Ubiquitin; D000251:Adenosine Triphosphatases