SAD: a presynaptic kinase associated with synaptic vesicles and the active zone cytomatrix that regulates neurotransmitter release.
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.
Inoue
Eiji
E
KAN Research Institute, Kyoto 600-8815, Japan.
Mochida
Sumiko
S
Takagi
Hiroshi
H
Higa
Susumu
S
Deguchi-Tawarada
Maki
M
Takao-Rikitsu
Etsuko
E
Inoue
Marie
M
Yao
Ikuko
I
Takeuchi
Kosei
K
Kitajima
Isao
I
Setou
Mitsutoshi
M
Ohtsuka
Toshihisa
T
Takai
Yoshimi
Y
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
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