title: Molecular insights into vesicle tethering at the Golgi by the conserved oligomeric Golgi (COG) complex and the golgin TATA element modulatory factor (TMF).
abstract: Protein sorting between eukaryotic compartments requires vesicular transport, wherein tethering provides the first contact between vesicle and target membranes. Here we map and start to functionally analyze the interaction network of the conserved oligomeric Golgi (COG) complex that mediates retrograde tethering at the Golgi. The interactions of COG subunits with members of transport factor families assign the individual subunits as specific interaction hubs. Functional analysis of selected interactions suggests a mechanistic tethering model. We find that the COG complex interacts with two different Rabs in addition to each end of the golgin "TATA element modulatory factor" (TMF). This allows COG to potentially bridge the distance between the distal end of the golgin and the target membrane thereby promoting tighter docking. Concurrently we show that the central portion of TMF can bind to Golgi membranes that are liberated of their COPI cover. This latter interaction could serve to bring vesicle and target membranes into close apposition prior to fusion. A target selection mechanism, in which a hetero-oligomeric tethering factor organizes Rabs and coiled transport factors to enable protein sorting specificity, could be applicable to vesicle targeting throughout eukaryotic cells.
authors.affiliation: Department of Biology, University of York, York, YO10 5DD, United Kingdom.
authors.forename: Victoria J
authors.initials: VJ
authors.lastname: Miller
authors.forename: Prateek
authors.initials: P
authors.lastname: Sharma
authors.forename: Tetyana A
authors.initials: TA
authors.lastname: Kudlyk
authors.forename: Laura
authors.initials: L
authors.lastname: Frost
authors.forename: Adam P
authors.initials: AP
authors.lastname: Rofe
authors.forename: Irene J
authors.initials: IJ
authors.lastname: Watson
authors.forename: Rainer
authors.initials: R
authors.lastname: Duden
authors.forename: Martin
authors.initials: M
authors.lastname: Lowe
authors.forename: Vladimir V
authors.initials: VV
authors.lastname: Lupashin
authors.forename: Daniel
authors.initials: D
authors.lastname: Ungar
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport / Q000235:genetics / Q000378:metabolism*; D020755:Coat Protein Complex I / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D006056:Golgi Apparatus / Q000235:genetics / Q000378:metabolism*; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D007425:Intracellular Membranes / Q000378:metabolism*; D046912:Multiprotein Complexes / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D021381:Protein Transport / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D020691:rab GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; D020755:Coat Protein Complex I; D004268:DNA-Binding Proteins; D046912:Multiprotein Complexes; D014157:Transcription Factors; C077335:TMF1 protein, human; D020691:rab GTP-Binding Proteins