title: RIM1alpha forms a protein scaffold for regulating neurotransmitter release at the active zone.
abstract: Neurotransmitters are released by synaptic vesicle fusion at the active zone. The active zone of a synapse mediates Ca2+-triggered neurotransmitter release, and integrates presynaptic signals in regulating this release. Much is known about the structure of active zones and synaptic vesicles, but the functional relation between their components is poorly understood. Here we show that RIM1alpha, an active zone protein that was identified as a putative effector for the synaptic vesicle protein Rab3A, interacts with several active zone molecules, including Munc13-1 (ref. 6) and alpha-liprins, to form a protein scaffold in the presynaptic nerve terminal. Abolishing the expression of RIM1alpha in mice shows that RIM1alpha is essential for maintaining normal probability of neurotransmitter release, and for regulating release during short-term synaptic plasticity. These data indicate that RIM1alpha has a central function in integrating active zone proteins and synaptic vesicles into a molecular scaffold that controls neurotransmitter release.
authors.affiliation: The Center for Basic Neuroscience and Department of Molecular Genetics, Howard Hughes Medical Institute, The University of Texas Southwestern Medical Center, Dallas, Texas 75390-9111, USA.
authors.forename: Susanne
authors.initials: S
authors.lastname: Schoch
authors.forename: Pablo E
authors.initials: PE
authors.lastname: Castillo
authors.forename: Tobias
authors.initials: T
authors.lastname: Jo
authors.forename: Konark
authors.initials: K
authors.lastname: Mukherjee
authors.forename: Martin
authors.initials: M
authors.lastname: Geppert
authors.forename: Yun
authors.initials: Y
authors.lastname: Wang
authors.forename: Frank
authors.initials: F
authors.lastname: Schmitz
authors.forename: Robert C
authors.initials: RC
authors.lastname: Malenka
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Südhof
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D001921:Brain / Q000378:metabolism; D019556:COS Cells; D016291:Dizocilpine Maleate; D019204:GTP-Binding Proteins; D066298:In Vitro Techniques; D047908:Intracellular Signaling Peptides and Proteins; D046911:Macromolecular Substances; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D009473:Neuronal Plasticity; D018377:Neurotransmitter Agents / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism / Q000502:physiology; D017729:Presynaptic Terminals / Q000378:metabolism / Q000502:physiology*; D011485:Protein Binding; D020033:Protein Isoforms / Q000235:genetics; D020826:rab3A GTP-Binding Protein / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D047908:Intracellular Signaling Peptides and Proteins; D046911:Macromolecular Substances; D009419:Nerve Tissue Proteins; D018377:Neurotransmitter Agents; D010750:Phosphoproteins; C490599:Ppfia4 protein, rat; D020033:Protein Isoforms; C491492:RIMS1 protein, human; C107293:Rim protein, mammalian; C491490:Rims1 protein, mouse; C491489:Rims1 protein, rat; C485548:UNC13B protein, human; C485549:Unc13b protein, mouse; C485550:Unc13c protein, mouse; D016291:Dizocilpine Maleate; D019204:GTP-Binding Proteins; D020826:rab3A GTP-Binding Protein