title: How to Make an Active Zone: Unexpected Universal Functional Redundancy between RIMs and RIM-BPs.
abstract: RIMs and RIM-binding proteins (RBPs) are evolutionary conserved multidomain proteins of presynaptic active zones that are known to recruit Ca(2+) channels; in addition, RIMs perform well-recognized functions in tethering and priming synaptic vesicles for exocytosis. However, deletions of RIMs or RBPs in mice cause only partial impairments in various active zone functions and have no effect on active zone structure, as visualized by electron micrographs, suggesting that their contribution to active zone functions is limited. Here, we show in synapses of the calyx of Held in vivo and hippocampal neurons in culture that combined, but not individual, deletions of RIMs and RBPs eliminate tethering and priming of synaptic vesicles, deplete presynaptic Ca(2+) channels, and ablate active zone complexes, as analyzed by electron microscopy of chemically fixed synapses. Thus, RBPs perform unexpectedly broad roles at the active zone that together with those of RIMs are essential for all active zone functions.
authors.affiliation: Department of Cellular and Molecular Physiology and Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA 94305, USA. Electronic address: claudioa@stanford.edu.
authors.forename: Claudio
authors.initials: C
authors.lastname: Acuna
authors.affiliation: Department of Cell Biology, Yale University School of Medicine, New Haven, CT 06510, USA.
authors.forename: Xinran
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Cellular and Molecular Physiology and Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA 94305, USA. Electronic address: tcs1@stanford.edu.
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Südhof
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D019204:GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D017729:Presynaptic Terminals / Q000378:metabolism / Q000648:ultrastructure; D054840:Retinol-Binding Proteins, Cellular / Q000235:genetics / Q000378:metabolism*; D013569:Synapses / Q000378:metabolism / Q000648:ultrastructure; D013572:Synaptic Vesicles / Q000378:metabolism; D065833:Trapezoid Body / Q000378:metabolism*
chemical_list: D009419:Nerve Tissue Proteins; C518457:Rbp1 protein, mouse; C518460:Rbp2 protein, mouse; D054840:Retinol-Binding Proteins, Cellular; C491490:Rims1 protein, mouse; C491491:Rims2 protein, mouse; C503321:Unc13a protein, mouse; D019204:GTP-Binding Proteins; D002118:Calcium