title: The exomer coat complex transports Fus1p to the plasma membrane via a novel plasma membrane sorting signal in yeast.
abstract: Sorting of transmembrane cargo proteins to different cellular compartments is mediated by sorting signals that are recognized by coat proteins involved in vesicle biogenesis. We have identified a sorting signal in the yeast cell fusion protein Fus1p that is required for its transport from the trans-Golgi compartment to the plasma membrane. Transport of Fus1p from the trans-Golgi to the cell surface is dependent on Chs5p, a component of the multisubunit exomer complex. We show that Fus1p transport is also dependent on the exomer components Bch1p and Bud7p. Disruption of the clathrin adaptor protein complex 1 (AP-1) restores Fus1p localization to the cell surface in the absence of exomer, possibly by promoting an alternate, exomer-independent route of transport. Mutation of an IXTPK sequence in the cytosolic tail of Fus1p abolishes its physical interaction with Chs5p, results in mislocalization of Fus1p, and therefore causes a cell fusion defect. These defects are suppressed by disruption of AP-1. We suggest that IXTPK comprises a novel sorting signal that is recognized and bound by exomer leading to the capture of Fus1p into coated vesicles en route to the cell surface.
authors.affiliation: Department of Molecular and Cell Biology and Howard Hughes Medical Institute, University of California, Berkeley, Berkeley, CA, 94720, USA.
authors.forename: Robyn M
authors.initials: RM
authors.lastname: Barfield
authors.forename: J Christopher
authors.initials: JC
authors.lastname: Fromme
authors.forename: Randy
authors.initials: R
authors.lastname: Schekman
mesh_terms: D000595:Amino Acid Sequence; D002462:Cell Membrane / Q000378:metabolism*; D002687:Chitin Synthase / Q000235:genetics / Q000378:metabolism; D018699:Coated Vesicles / Q000378:metabolism; D005089:Exocytosis / Q000502:physiology*; D008561:Membrane Fusion / Q000502:physiology*; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D009154:Mutation; D021382:Protein Sorting Signals; D021381:Protein Transport; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D016415:Sequence Alignment; D018808:Transcription Factor AP-1 / Q000235:genetics / Q000378:metabolism; D020798:Two-Hybrid System Techniques; D021601:trans-Golgi Network / Q000378:metabolism
chemical_list: C490024:FUS1 protein, S cerevisiae; D008565:Membrane Proteins; D021382:Protein Sorting Signals; D011993:Recombinant Fusion Proteins; D029701:Saccharomyces cerevisiae Proteins; D018808:Transcription Factor AP-1; C491360:CHS5 protein, S cerevisiae; D002687:Chitin Synthase