title: A functional role for the GCC185 golgin in mannose 6-phosphate receptor recycling.
abstract: Mannose 6-phosphate receptors (MPRs) deliver newly synthesized lysosomal enzymes to endosomes and then recycle to the Golgi. MPR recycling requires Rab9 GTPase; Rab9 recruits the cytosolic adaptor TIP47 and enhances its ability to bind to MPR cytoplasmic domains during transport vesicle formation. Rab9-bearing vesicles then fuse with the trans-Golgi network (TGN) in living cells, but nothing is known about how these vesicles identify and dock with their target. We show here that GCC185, a member of the Golgin family of putative tethering proteins, is a Rab9 effector that is required for MPR recycling from endosomes to the TGN in living cells, and in vitro. GCC185 does not rely on Rab9 for its TGN localization; depletion of GCC185 slightly alters the Golgi ribbon but does not interfere with Golgi function. Loss of GCC185 triggers enhanced degradation of mannose 6-phosphate receptors and enhanced secretion of hexosaminidase. These data assign a specific pathway to an interesting, TGN-localized protein and suggest that GCC185 may participate in the docking of late endosome-derived, Rab9-bearing transport vesicles at the TGN.
authors.affiliation: Department of Biochemistry, Stanford University School of Medicine, Stanford, CA 94305-5307, USA.
authors.forename: Jonathan V
authors.initials: JV
authors.lastname: Reddy
authors.forename: Alondra Schweizer
authors.initials: AS
authors.lastname: Burguete
authors.forename: Khambhampaty
authors.initials: K
authors.lastname: Sridevi
authors.forename: Ian G
authors.initials: IG
authors.lastname: Ganley
authors.forename: Ryan M
authors.initials: RM
authors.lastname: Nottingham
authors.forename: Suzanne R
authors.initials: SR
authors.lastname: Pfeffer
mesh_terms: D018797:Cell Cycle Proteins / Q000378:metabolism; D011992:Endosomes / Q000378:metabolism; D006056:Golgi Apparatus / Q000378:metabolism* / Q000648:ultrastructure; D000077614:Golgi Matrix Proteins; D006367:HeLa Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins / Q000378:metabolism / Q000502:physiology*; D008954:Models, Biological; D034741:RNA, Small Interfering; D017527:Receptor, IGF Type 2 / Q000378:metabolism*; D014162:Transfection; D022161:Transport Vesicles / Q000378:metabolism; D021601:trans-Golgi Network / Q000378:metabolism* / Q000648:ultrastructure
chemical_list: D018797:Cell Cycle Proteins; C472299:GCC2 protein, human; D000077614:Golgi Matrix Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D034741:RNA, Small Interfering; D017527:Receptor, IGF Type 2; C069930:rad9 protein