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 p...

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Bibliographic Details
Published in:Neuron (Cambridge, Mass.) Mass.), 2006-04, Vol.50 (2), p.261-275
Main Authors: Inoue, Eiji, Mochida, Sumiko, Takagi, Hiroshi, Higa, Susumu, Deguchi-Tawarada, Maki, Takao-Rikitsu, Etsuko, Inoue, Marie, Yao, Ikuko, Takeuchi, Kosei, Kitajima, Isao, Setou, Mitsutoshi, Ohtsuka, Toshihisa, Takai, Yoshimi
Format: Article
Language:English
Subjects:
Animals
Blotting, Northern
Brain research
CELLBIO
Cells, Cultured
Cloning, Molecular
Excitatory Postsynaptic Potentials - physiology
Hippocampus - metabolism
Humans
Intracellular Signaling Peptides and Proteins
Isoenzymes - genetics
Isoenzymes - metabolism
Kinases
Microscopy, Immunoelectron
Molecular weight
MOLNEURO
Neurons - metabolism
Neurons - ultrastructure
Neurotransmitter Agents - secretion
Phosphorylation
Protein-Serine-Threonine Kinases - genetics
Protein-Serine-Threonine Kinases - metabolism
Proteins
Rats
Rodents
Science
SIGNALING
Software
Synaptic Transmission - physiology
Synaptic Vesicles - metabolism
Synaptic Vesicles - ultrastructure
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Summary: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.
ISSN:0896-6273
1097-4199
DOI:10.1016/j.neuron.2006.03.018