title: Multiple roles for the active zone protein RIM1alpha in late stages of neurotransmitter release.
abstract: The active zone protein RIM1alpha interacts with multiple active zone and synaptic vesicle proteins and is implicated in short- and long-term synaptic plasticity, but it is unclear how RIM1alpha's biochemical interactions translate into physiological functions. To address this question, we analyzed synaptic transmission in autaptic neurons cultured from RIM1alpha-/- mice. Deletion of RIM1alpha causes a large reduction in the readily releasable pool of vesicles, alters short-term plasticity, and changes the properties of evoked asynchronous release. Lack of RIM1alpha, however, had no effect on synapse formation, spontaneous release, overall Ca2+ sensitivity of release, or synaptic vesicle recycling. These results suggest that RIM1alpha modulates sequential steps in synaptic vesicle exocytosis through serial protein-protein interactions and that this modulation is the basis for RIM1alpha's role in synaptic plasticity.
authors.affiliation: Nancy Pritzker Laboratory, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Palo Alto, CA 94304, USA.
authors.forename: Nicole
authors.initials: N
authors.lastname: Calakos
authors.forename: Susanne
authors.initials: S
authors.lastname: Schoch
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Südhof
authors.forename: Robert C
authors.initials: RC
authors.lastname: Malenka
mesh_terms: D000241:Adenosine / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D015153:Blotting, Western / Q000379:methods; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D004558:Electric Stimulation / Q000379:methods; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000235:genetics / Q000502:physiology / Q000528:radiation effects; D019204:GTP-Binding Proteins / Q000235:genetics / Q000502:physiology*; D006624:Hippocampus / Q000166:cytology; D006982:Hypertonic Solutions / Q000494:pharmacology; D007150:Immunohistochemistry / Q000379:methods; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D051379:Mice; D018345:Mice, Knockout; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000502:physiology*; D009433:Neural Inhibition / Q000187:drug effects; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D018377:Neurotransmitter Agents / Q000378:metabolism*; D018408:Patch-Clamp Techniques / Q000379:methods; D010703:Phorbol Esters / Q000494:pharmacology; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism* / Q000528:radiation effects; D013324:Strontium / Q000494:pharmacology; D013395:Sucrose; D016704:Synapsins / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D013572:Synaptic Vesicles / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D020692:rab3 GTP-Binding Proteins / Q000378:metabolism
chemical_list: D006982:Hypertonic Solutions; D008869:Microtubule-Associated Proteins; D009419:Nerve Tissue Proteins; D018377:Neurotransmitter Agents; D010703:Phorbol Esters; C107293:Rim protein, mammalian; C491490:Rims1 protein, mouse; D016704:Synapsins; D013395:Sucrose; D019204:GTP-Binding Proteins; C475524:Rim2 protein, mouse; D020692:rab3 GTP-Binding Proteins; D000241:Adenosine; D002118:Calcium; D013324:Strontium