title: SAD: a presynaptic kinase associated with synaptic vesicles and the active zone cytomatrix that regulates neurotransmitter release.
abstract: A serine/threonine kinase SAD-1 in C. elegans regulates synapse development. We report here the isolation and characterization of mammalian orthologs of SAD-1, named SAD-A and SAD-B, which are specifically expressed in the brain. SAD-B is associated with synaptic vesicles and, like the active zone proteins CAST and Bassoon, is tightly associated with the presynaptic cytomatrix in nerve terminals. A short conserved region (SCR) in the COOH-terminus is required for the synaptic localization of SAD-B. Overexpression of SAD-B in cultured rat hippocampal neurons significantly increases the frequency of miniature excitatory postsynaptic current but not its amplitude. Introduction of SCR into presynaptic superior cervical ganglion neurons in culture significantly inhibits evoked synaptic transmission. Moreover, SCR decreases the size of the readily releasable pool measured by applying hypertonic sucrose. Furthermore, SAD-B phosphorylates the active zone protein RIM1 but not Munc13-1. These results suggest that mammalian SAD kinase presynaptically regulates neurotransmitter release.
authors.affiliation: KAN Research Institute, Kyoto 600-8815, Japan.
authors.forename: Eiji
authors.initials: E
authors.lastname: Inoue
authors.forename: Sumiko
authors.initials: S
authors.lastname: Mochida
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Takagi
authors.forename: Susumu
authors.initials: S
authors.lastname: Higa
authors.forename: Maki
authors.initials: M
authors.lastname: Deguchi-Tawarada
authors.forename: Etsuko
authors.initials: E
authors.lastname: Takao-Rikitsu
authors.forename: Marie
authors.initials: M
authors.lastname: Inoue
authors.forename: Ikuko
authors.initials: I
authors.lastname: Yao
authors.forename: Kosei
authors.initials: K
authors.lastname: Takeuchi
authors.forename: Isao
authors.initials: I
authors.lastname: Kitajima
authors.forename: Mitsutoshi
authors.initials: M
authors.lastname: Setou
authors.forename: Toshihisa
authors.initials: T
authors.lastname: Ohtsuka
authors.forename: Yoshimi
authors.initials: Y
authors.lastname: Takai
mesh_terms: D000818:Animals; D015152:Blotting, Northern; D002478:Cells, Cultured; D003001:Cloning, Molecular; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D006624:Hippocampus / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D016253:Microscopy, Immunoelectron; D009474:Neurons / Q000378:metabolism* / Q000648:ultrastructure; D018377:Neurotransmitter Agents / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D009435:Synaptic Transmission / Q000502:physiology; D013572:Synaptic Vesicles / Q000378:metabolism* / Q000648:ultrastructure
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D007527:Isoenzymes; D018377:Neurotransmitter Agents; C421165:sad-1 protein, C elegans; C523084:BRSK1 protein, human; D017346:Protein Serine-Threonine Kinases