title: FIP1/RCP binding to Golgin-97 regulates retrograde transport from recycling endosomes to the trans-Golgi network.
abstract: Many proteins are retrieved to the trans-Golgi Network (TGN) from the endosomal system through several retrograde transport pathways to maintain the composition and function of the TGN. However, the molecular mechanisms involved in these distinct retrograde pathways remain to be fully understood. Here we have used fluorescence and electron microscopy as well as various functional transport assays to show that Rab11a/b and its binding protein FIP1/RCP are both required for the retrograde delivery of TGN38 and Shiga toxin from early/recycling endosomes to the TGN, but not for the retrieval of mannose-6-phosphate receptor from late endosomes. Furthermore, by proteomic analysis we identified Golgin-97 as a FIP1/RCP-binding protein. The FIP1/RCP-binding domain maps to the C-terminus of Golgin-97, adjacent to its GRIP domain. Binding of FIP1/RCP to Golgin-97 does not affect Golgin-97 recruitment to the TGN, but appears to regulate the targeting of retrograde transport vesicles to the TGN. Thus, we propose that FIP1/RCP binding to Golgin-97 is required for tethering and fusion of recycling endosome-derived retrograde transport vesicles to the TGN.
authors.affiliation: Department of Cell and Developmental Biology, School of Medicine, University of Colorado Denver, Aurora, CO 80045, USA.
authors.forename: Jian
authors.initials: J
authors.lastname: Jing
authors.forename: Jagath R
authors.initials: JR
authors.lastname: Junutula
authors.forename: Christine
authors.initials: C
authors.lastname: Wu
authors.forename: Jemima
authors.initials: J
authors.lastname: Burden
authors.forename: Hugo
authors.initials: H
authors.lastname: Matern
authors.forename: Andrew A
authors.initials: AA
authors.lastname: Peden
authors.forename: Rytis
authors.initials: R
authors.lastname: Prekeris
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000172:deficiency / Q000378:metabolism*; D033942:Adaptor Proteins, Vesicular Transport / Q000378:metabolism; D001324:Autoantigens / Q000378:metabolism*; D004705:Endocytosis; D011992:Endosomes / Q000378:metabolism* / Q000648:ultrastructure; D055785:Gene Knockdown Techniques; D000077614:Golgi Matrix Proteins; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D008562:Membrane Glycoproteins / Q000378:metabolism; D008565:Membrane Proteins / Q000172:deficiency / Q000378:metabolism*; D008954:Models, Biological; D011485:Protein Binding; D025941:Protein Interaction Mapping; D021381:Protein Transport; D011990:Receptors, Transferrin / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D022621:Shiga Toxin / Q000378:metabolism; D020691:rab GTP-Binding Proteins / Q000378:metabolism; D021601:trans-Golgi Network / Q000378:metabolism* / Q000648:ultrastructure; D000099193:rab11 GTP-Binding Proteins
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; D001324:Autoantigens; D000077614:Golgi Matrix Proteins; D049452:Green Fluorescent Proteins; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D011990:Receptors, Transferrin; D011993:Recombinant Fusion Proteins; D022621:Shiga Toxin; D020691:rab GTP-Binding Proteins; D000099193:rab11 GTP-Binding Proteins; C450721:Golgi complex autoantigen, 97-kDa; C488966:RAB11FIP1 protein, human; C072237:TGOLN2 protein, human; C114154:epsin