title: A syntaxin 10-SNARE complex distinguishes two distinct transport routes from endosomes to the trans-Golgi in human cells.
abstract: Mannose 6-phosphate receptors (MPRs) are transported from endosomes to the Golgi after delivering lysosomal enzymes to the endocytic pathway. This process requires Rab9 guanosine triphosphatase (GTPase) and the putative tether GCC185. We show in human cells that a soluble NSF attachment protein receptor (SNARE) complex comprised of syntaxin 10 (STX10), STX16, Vti1a, and VAMP3 is required for this MPR transport but not for the STX6-dependent transport of TGN46 or cholera toxin from early endosomes to the Golgi. Depletion of STX10 leads to MPR missorting and hypersecretion of hexosaminidase. Mouse and rat cells lack STX10 and, thus, must use a different target membrane SNARE for this process. GCC185 binds directly to STX16 and is competed by Rab6. These data support a model in which the GCC185 tether helps Rab9-bearing transport vesicles deliver their cargo to the trans-Golgi and suggest that Rab GTPases can regulate SNARE-tether interactions. Importantly, our data provide a clear molecular distinction between the transport of MPRs and TGN46 to the trans-Golgi.
authors.affiliation: Department of Biochemistry, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Ian G
authors.initials: IG
authors.lastname: Ganley
authors.forename: Eric
authors.initials: E
authors.lastname: Espinosa
authors.forename: Suzanne R
authors.initials: SR
authors.lastname: Pfeffer
mesh_terms: D001667:Binding, Competitive; D002460:Cell Line; D002772:Cholera Toxin / Q000378:metabolism; D011992:Endosomes / Q000378:metabolism*; D000077614:Golgi Matrix Proteins; D006801:Humans; D008562:Membrane Glycoproteins / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D021381:Protein Transport / Q000502:physiology; D050765:Qa-SNARE Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D017527:Receptor, IGF Type 2 / Q000378:metabolism; D050600:SNARE Proteins / Q000502:physiology*; D051438:Syntaxin 16 / Q000378:metabolism / Q000502:physiology; D020691:rab GTP-Binding Proteins / Q000378:metabolism; D021601:trans-Golgi Network / Q000378:metabolism*
chemical_list: C472299:GCC2 protein, human; D000077614:Golgi Matrix Proteins; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D050765:Qa-SNARE Proteins; C094135:Rab6 protein; D017527:Receptor, IGF Type 2; D050600:SNARE Proteins; C496118:STX16 protein, human; D051438:Syntaxin 16; C072237:TGOLN2 protein, human; D002772:Cholera Toxin; D020691:rab GTP-Binding Proteins