title: Rab6-interacting protein 1 links Rab6 and Rab11 function.
abstract: Rab11 and Rab6 guanosine triphosphatases are associated with membranes of the recycling endosomes (REs) and Golgi complex, respectively. Evidence indicates that they sequentially regulate a retrograde transport pathway between these two compartments, suggesting the existence of proteins that must co-ordinate their functions. Here, we report the characterization of two isoforms of a protein, Rab6-interacting protein 1 (R6IP1), originally identified as a Rab6-binding protein. R6IP1 also binds to Rab11A in its GTP-bound conformation. In interphase cells, R6IP1 is targeted to the Golgi in a Rab6-dependent manner but can associate with Rab11-positive compartments when the level of Rab11A is increased within the cells. Fluorescence resonance energy transfer analysis using fluorescence lifetime imaging shows that the overexpression of R6IP1 promotes an interaction between Rab11A and Rab6 in living cells. Accordingly, the REs marked by Rab11 and transferrin receptor are depleted from the cell periphery and accumulate in the pericentriolar area. However, endosomal and Golgi membranes do not appear to fuse with each other. We also show that R6IP1 function is required during metaphase and cytokinesis, two mitotic steps in which a role of Rab6 and Rab11 has been previously documented. We propose that R6IP1 may couple Rab6 and Rab11 function throughout the cell cycle.
authors.affiliation: Institut Curie, Centre de Recherche, Paris, 75248 France.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Miserey-Lenkei
authors.forename: François
authors.initials: F
authors.lastname: Waharte
authors.forename: Annick
authors.initials: A
authors.lastname: Boulet
authors.forename: Marie-Hélène
authors.initials: MH
authors.lastname: Cuif
authors.forename: Danielle
authors.initials: D
authors.lastname: Tenza
authors.forename: Amed
authors.initials: A
authors.lastname: El Marjou
authors.forename: Graça
authors.initials: G
authors.lastname: Raposo
authors.forename: Jean
authors.initials: J
authors.lastname: Salamero
authors.forename: Laurent
authors.initials: L
authors.lastname: Héliot
authors.forename: Bruno
authors.initials: B
authors.lastname: Goud
authors.forename: Solange
authors.initials: S
authors.lastname: Monier
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D000818:Animals; D002453:Cell Cycle / Q000235:genetics / Q000502:physiology; D002460:Cell Line; D006056:Golgi Apparatus / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D011817:Rabbits; D018411:Spodoptera / Q000235:genetics; D020691:rab GTP-Binding Proteins / Q000378:metabolism* / Q000502:physiology; D000099193:rab11 GTP-Binding Proteins
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D020691:rab GTP-Binding Proteins; D000099193:rab11 GTP-Binding Proteins; C094135:Rab6 protein