Rab1 interaction with a GM130 effector complex regulates COPII vesicle cis--Golgi tethering.
Members of the Rab family of small molecular weight GTPases regulate the fusion of transport intermediates to target membranes along the biosynthetic and endocytic pathways. We recently demonstrated that Rab1 recruitment of the tethering factor p115 into a cis-SNARE complex programs coat protein II vesicles budding from the endoplasmic reticulum (donor compartment) for fusion with the Golgi apparatus (acceptor compartment) (Allan BB, Moyer BD, Balch WE. Science 2000; 289: 444-448). However, the molecular mechanism(s) of Rab regulation of Golgi acceptor compartment function in endoplasmic reticulum to Golgi transport are unknown. Here, we demonstrate that the cis-Golgi tethering protein GM130, complexed with GRASP65 and other proteins, forms a novel Rab1 effector complex that interacts with activated Rab1-GTP in a p115-independent manner and is required for coat protein II vesicle targeting/fusion with the cis-Golgi. We propose a 'homing hypothesis' in which the same Rab interacts with distinct tethering factors at donor and acceptor membranes to program heterotypic membrane fusion events between transport intermediates and their target compartments.
Moyer
B D
BD
Department of Cell and Molecular Biology, The Institute for Childhood and Neglected Diseases, The Scripps Research Institute, 10550 N. Torrey Pines Road, San Diego, California 92037, USA.
Allan
B B
BB
Balch
W E
WE
D000818:Animals; D001324:Autoantigens; D001693:Biological Transport, Active; D022181:COP-Coated Vesicles / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism / Q000502:physiology; D002460:Cell Line; D004721:Endoplasmic Reticulum / Q000378:metabolism; D006056:Golgi Apparatus / Q000378:metabolism*; D000077614:Golgi Matrix Proteins; D020730:Guanine Nucleotide Dissociation Inhibitors / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000378:metabolism; D007668:Kidney; D008099:Liver; D046911:Macromolecular Substances; D008561:Membrane Fusion; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology; D008856:Microscopy, Fluorescence; D008954:Models, Biological; D010750:Phosphoproteins / Q000378:metabolism; D011485:Protein Binding; D051381:Rats; D029701:Saccharomyces cerevisiae Proteins; D013379:Substrate Specificity; D033921:Vesicular Transport Proteins; D020761:rab1 GTP-Binding Proteins / Q000378:metabolism*
D001324:Autoantigens; D002352:Carrier Proteins; C086796:GDP dissociation inhibitor 1; D000077614:Golgi Matrix Proteins; C097741:Golgin subfamily A member 2; C491577:Gorasp1 protein, rat; D020730:Guanine Nucleotide Dissociation Inhibitors; D046911:Macromolecular Substances; D008565:Membrane Proteins; D010750:Phosphoproteins; C106113:SEC31 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D033921:Vesicular Transport Proteins; C091580:vesicular transport factor p115; D006160:Guanosine Triphosphate; D020761:rab1 GTP-Binding Proteins