title: C4orf41 and TTC-15 are mammalian TRAPP components with a role at an early stage in ER-to-Golgi trafficking.
abstract: TRAPP is a multisubunit tethering complex implicated in multiple vesicle trafficking steps in Saccharomyces cerevisiae and conserved throughout eukarya, including humans. Here we confirm the role of TRAPPC2L as a stable component of mammalian TRAPP and report the identification of four novel components of the complex: C4orf41, TTC-15, KIAA1012, and Bet3L. Two of the components, KIAA1012 and Bet3L, are mammalian homologues of Trs85p and Bet3p, respectively. The remaining two novel TRAPP components, C4orf41 and TTC-15, have no homologues in S. cerevisiae. With this work, human homologues of all the S. cerevisiae TRAPP proteins, with the exception of the Saccharomycotina-specific subunit Trs65p, have now been reported. Through a multidisciplinary approach, we demonstrate that the novel proteins are bona fide components of human TRAPP and implicate C4orf41 and TTC-15 (which we call TRAPPC11 and TRAPPC12, respectively) in ER-to-Golgi trafficking at a very early stage. We further present a binary interaction map for all known mammalian TRAPP components and evidence that TRAPP oligomerizes. Our data are consistent with the absence of a TRAPP I-equivalent complex in mammalian cells, suggesting that the fundamental unit of mammalian TRAPP is distinct from that characterized in S. cerevisiae.
authors.affiliation: Department of Biology, Concordia University, Montreal, Quebec, Canada.
authors.forename: P James
authors.initials: PJ
authors.lastname: Scrivens
authors.forename: Baraa
authors.initials: B
authors.lastname: Noueihed
authors.forename: Nassim
authors.initials: N
authors.lastname: Shahrzad
authors.forename: Sokunthear
authors.initials: S
authors.lastname: Hul
authors.forename: Stephanie
authors.initials: S
authors.lastname: Brunet
authors.forename: Michael
authors.initials: M
authors.lastname: Sacher
mesh_terms: D004721:Endoplasmic Reticulum / Q000378:metabolism*; D006056:Golgi Apparatus / Q000378:metabolism*; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism; D021381:Protein Transport; D034622:RNA Interference; D034741:RNA, Small Interfering; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D033921:Vesicular Transport Proteins / Q000235:genetics* / Q000378:metabolism*
chemical_list: C098389:BET3 protein, S cerevisiae; D008565:Membrane Proteins; D034741:RNA, Small Interfering; D029701:Saccharomyces cerevisiae Proteins; C000613447:TRAPPC11 protein, human; D033921:Vesicular Transport Proteins; C406327:transport protein particle, TRAPP