title: GCC185 plays independent roles in Golgi structure maintenance and AP-1-mediated vesicle tethering.
abstract: GCC185 is a long coiled-coil protein localized to the trans-Golgi network (TGN) that functions in maintaining Golgi structure and tethering mannose 6-phosphate receptor (MPR)-containing transport vesicles en route to the Golgi. We report the identification of two distinct domains of GCC185 needed either for Golgi structure maintenance or transport vesicle tethering, demonstrating the independence of these two functions. The domain needed for vesicle tethering binds to the clathrin adaptor AP-1, and cells depleted of GCC185 accumulate MPRs in transport vesicles that are AP-1 decorated. This study supports a previously proposed role of AP-1 in retrograde transport of MPRs from late endosomes to the Golgi and indicates that docking may involve the interaction of vesicle-associated AP-1 protein with the TGN-associated tethering protein GCC185.
authors.affiliation: Department of Biochemistry, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Frank C
authors.initials: FC
authors.lastname: Brown
authors.forename: Carmel H
authors.initials: CH
authors.lastname: Schindelhaim
authors.forename: Suzanne R
authors.initials: SR
authors.lastname: Pfeffer
mesh_terms: D033961:Adaptor Protein Complex 1 / Q000378:metabolism*; D000818:Animals; D002417:Cattle; D002460:Cell Line; D002522:Chlorocebus aethiops; D004847:Epithelial Cells / Q000378:metabolism; D006056:Golgi Apparatus / Q000473:pathology / Q000502:physiology*; D000077614:Golgi Matrix Proteins; D006367:HeLa Cells; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D011485:Protein Binding / Q000502:physiology; D054730:Protein Interaction Domains and Motifs / Q000502:physiology; D021381:Protein Transport / Q000502:physiology*; D034741:RNA, Small Interfering / Q000235:genetics; D017527:Receptor, IGF Type 2 / Q000378:metabolism; D017384:Sequence Deletion / Q000502:physiology; D014162:Transfection; D022161:Transport Vesicles / Q000502:physiology*; D033921:Vesicular Transport Proteins / Q000378:metabolism; D021601:trans-Golgi Network / Q000502:physiology
chemical_list: D033961:Adaptor Protein Complex 1; C497850:CLASP1 protein, human; C497851:CLASP2 protein, human; C472299:GCC2 protein, human; D000077614:Golgi Matrix Proteins; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; D034741:RNA, Small Interfering; D017527:Receptor, IGF Type 2; D033921:Vesicular Transport Proteins; C093846:early endosome antigen 1