title: The BLOC-1 complex promotes endosomal maturation by recruiting the Rab5 GTPase-activating protein Msb3.
abstract: Membrane microcompartments of the early endosomes serve as a sorting and signaling platform, where receptors are either recycled back to the plasma membrane or forwarded to the lysosome for destruction. In metazoan cells, three complexes, termed BLOC-1 to -3, mediate protein sorting from the early endosome to lysosomes and lysosome-related organelles. We now demonstrate that BLOC-1 is an endosomal Rab-GAP (GTPase-activating protein) adapter complex in yeast. The yeast BLOC-1 consisted of six subunits, which localized interdependently to the endosomes in a Rab5/Vps21-dependent manner. In the absence of BLOC-1 subunits, the balance between recycling and degradation of selected cargoes was impaired. Additionally, our data show that BLOC-1 is both a Vps21 effector and an adapter for its GAP Msb3. BLOC-1 and Msb3 interacted in vivo, and both mutants resulted in a redistribution of active Vps21 to the vacuole surface. We thus conclude that BLOC-1 controls the lifetime of active Rab5/Vps21 and thus endosomal maturation along the endocytic pathway.
authors.affiliation: Department of Biology/Chemistry, Biochemistry Section, University of Osnabrück, 49076 Osnabrück, Germany.
authors.forename: Arun T
authors.initials: AT
authors.lastname: John Peter
authors.forename: Jens
authors.initials: J
authors.lastname: Lachmann
authors.forename: Meenakshi
authors.initials: M
authors.lastname: Rana
authors.forename: Madeleine
authors.initials: M
authors.lastname: Bunge
authors.forename: Margarita
authors.initials: M
authors.lastname: Cabrera
authors.forename: Christian
authors.initials: C
authors.lastname: Ungermann
mesh_terms: D004705:Endocytosis / Q000502:physiology; D011992:Endosomes / Q000235:genetics / Q000378:metabolism*; D020690:GTPase-Activating Proteins / Q000235:genetics / Q000378:metabolism*; D046912:Multiprotein Complexes / Q000235:genetics / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D014617:Vacuoles / Q000235:genetics / Q000378:metabolism; D020691:rab GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D020696:rab5 GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D020690:GTPase-Activating Proteins; C540987:MSB3 protein, S cerevisiae; D046912:Multiprotein Complexes; D029701:Saccharomyces cerevisiae Proteins; C086866:VPS21 protein, S cerevisiae; D020691:rab GTP-Binding Proteins; D020696:rab5 GTP-Binding Proteins
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