Rab6-interacting protein 1 links Rab6 and Rab11 function.
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.
Miserey-Lenkei
Stéphanie
S
Institut Curie, Centre de Recherche, Paris, 75248 France.
Waharte
François
F
Boulet
Annick
A
Cuif
Marie-Hélène
MH
Tenza
Danielle
D
El Marjou
Amed
A
Raposo
Graça
G
Salamero
Jean
J
Héliot
Laurent
L
Goud
Bruno
B
Monier
Solange
S
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
D048868:Adaptor Proteins, Signal Transducing; D020691:rab GTP-Binding Proteins; D000099193:rab11 GTP-Binding Proteins; C094135:Rab6 protein