Multiple roles for the active zone protein RIM1alpha in late stages of neurotransmitter release.
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.
Calakos
Nicole
N
Nancy Pritzker Laboratory, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Palo Alto, CA 94304, USA.
Schoch
Susanne
S
Südhof
Thomas C
TC
Malenka
Robert C
RC
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
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