title: Global analysis of yeast endosomal transport identifies the vps55/68 sorting complex.
abstract: Endosomal transport is critical for cellular processes ranging from receptor down-regulation and retroviral budding to the immune response. A full understanding of endosome sorting requires a comprehensive picture of the multiprotein complexes that orchestrate vesicle formation and fusion. Here, we use unsupervised, large-scale phenotypic analysis and a novel computational approach for the global identification of endosomal transport factors. This technique effectively identifies components of known and novel protein assemblies. We report the characterization of a previously undescribed endosome sorting complex that contains two well-conserved proteins with four predicted membrane-spanning domains. Vps55p and Vps68p form a complex that acts with or downstream of ESCRT function to regulate endosomal trafficking. Loss of Vps68p disrupts recycling to the TGN as well as onward trafficking to the vacuole without preventing the formation of lumenal vesicles within the MVB. Our results suggest the Vps55/68 complex mediates a novel, conserved step in the endosomal maturation process.
authors.affiliation: Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, Department of Medical Genetics, University of British Columbia, Vancouver, BC V5Z 4H4, Canada.
authors.forename: Cayetana
authors.initials: C
authors.lastname: Schluter
authors.forename: Karen K Y
authors.initials: KK
authors.lastname: Lam
authors.forename: Jochen
authors.initials: J
authors.lastname: Brumm
authors.forename: Bella W
authors.initials: BW
authors.lastname: Wu
authors.forename: Matthew
authors.initials: M
authors.lastname: Saunders
authors.forename: Tom H
authors.initials: TH
authors.lastname: Stevens
authors.forename: Jennifer
authors.initials: J
authors.lastname: Bryan
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Conibear
mesh_terms: D001693:Biological Transport, Active; D002268:Carboxypeptidases / Q000235:genetics / Q000378:metabolism; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011992:Endosomes / Q000378:metabolism*; D017353:Gene Deletion; D020869:Gene Expression Profiling; D005800:Genes, Fungal; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D005810:Multigene Family; D046912:Multiprotein Complexes; D009154:Mutation; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D051964:Receptors, Mating Factor / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D033921:Vesicular Transport Proteins
chemical_list: D002352:Carrier Proteins; D008565:Membrane Proteins; D046912:Multiprotein Complexes; D051964:Receptors, Mating Factor; C081863:STE3 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D033921:Vesicular Transport Proteins; C468123:Vps55 protein, S cerevisiae; D002268:Carboxypeptidases; C520242:CPY protein, S cerevisiae