title: Rim is a putative Rab3 effector in regulating synaptic-vesicle fusion.
abstract: Rab3 is a neuronal GTP-binding protein that regulates fusion of synaptic vesicles and is essential for long-term potentiation of hippocampal mossy fibre synapses. More than thirty Rab GTP-binding proteins are known to function in diverse membrane transport pathways, although their mechanisms of action are unclear. We have now identified a putative Rab3-effector protein called Rim. Rim is composed of an amino-terminal zinc-finger motif and carboxy-terminal PDZ and C2 domains. It binds only to GTP (but not to GDP)-complexed Rab3, and interacts with no other Rab protein tested. There is enrichment of Rab3 and Rim in neurons, where they have complementary distributions. Rab3 is found only on synaptic vesicles, whereas Rim is localized to presynaptic active zones in conventional synapses, and to presynaptic ribbons in ribbon synapses. Transfection of PC12 cells with the amino-terminal domains of Rim greatly enhances regulated exocytosis in a Rab3-dependent manner. We propose that Rim serves as a Rab3-dependent regulator of synaptic-vesicle fusion by forming a GTP-dependent complex between synaptic plasma membranes and docked synaptic vesicles.
authors.affiliation: Department of Molecular Genetics, The University of Texas, Southwestern Medical Center at Dallas, 75235, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Wang
authors.forename: M
authors.initials: M
authors.lastname: Okamoto
authors.forename: F
authors.initials: F
authors.lastname: Schmitz
authors.forename: K
authors.initials: K
authors.lastname: Hofmann
authors.forename: T C
authors.initials: TC
authors.lastname: Südhof
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D005089:Exocytosis; D019204:GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D006160:Guanosine Triphosphate / Q000378:metabolism; D008561:Membrane Fusion; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism; D016716:PC12 Cells; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012160:Retina / Q000378:metabolism; D012441:Saccharomyces cerevisiae; D013116:Spinal Cord / Q000378:metabolism; D013347:Subcellular Fractions; D013570:Synaptic Membranes / Q000378:metabolism; D013572:Synaptic Vesicles / Q000378:metabolism*; D014162:Transfection; D033921:Vesicular Transport Proteins; D016335:Zinc Fingers; D020691:rab GTP-Binding Proteins; D020692:rab3 GTP-Binding Proteins; D000097624:Rabphilin-3A
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002118:Calcium; D019204:GTP-Binding Proteins; D006160:Guanosine Triphosphate; D009419:Nerve Tissue Proteins; D011993:Recombinant Fusion Proteins; D033921:Vesicular Transport Proteins; D020691:rab GTP-Binding Proteins; D020692:rab3 GTP-Binding Proteins; D000097624:Rabphilin-3A; C107293:Rim protein, mammalian; C491490:Rims1 protein, mouse; C491489:Rims1 protein, rat