2024-03-29T02:27:25Z
https://soar-ir.repo.nii.ac.jp/oai
oai:soar-ir.repo.nii.ac.jp:00012409
2022-12-14T04:01:32Z
1221:1222
A Single Amino Acid Mutation in SNAP-25 Induces Anxiety-Related Behavior in Mouse
Kataoka, Masakazu
Yamamori, Saori
Suzuki, Eiji
Watanabe, Shigeru
Sato, Taku
Miyaoka, Hitoshi
Azuma, Sadahiro
Ikegami, Shiro
Kuwahara, Reiko
Suzuki-Migishima, Rika
Nakahara, Yohko
Nihonmatsu, Itsuko
Inokuchi, Kaoru
Katoh-Fukui, Yuko
Yokoyama, Minesuke
Takahashi, Masami
PROTEIN-KINASE-C
ACTIVITY-DEPENDENT PHOSPHORYLATION
SYNAPTOSOME-ASSOCIATED PROTEIN
NEUROTRANSMITTER RELEASE
PHORBOL ESTER
MEMBRANE-FUSION
PC12 CELLS
RAT-BRAIN
EXOCYTOSIS
ENHANCEMENT
Synaptosomal-associated protein of 25 kDa (SNAP-25) is a presynaptic protein essential for neurotransmitter release. Previously, we demonstrate that protein kinase C (PKC) phosphorylates Ser(187) of SNAP-25, and enhances neurotransmitter release by recruiting secretory vesicles near to the plasma membrane. As PKC is abundant in the brain and SNAP-25 is essential for synaptic transmission, SNAP-25 phosphorylation is likely to play a crucial role in the central nervous system. We therefore generated a mutant mouse, substituting Ser(187) of SNAP-25 with Ala using "knock-in" technology. The most striking effect of the mutation was observed in their behavior. The homozygous mutant mice froze readily in response to environmental change, and showed strong anxiety-related behavior in general activity and light and dark preference tests. In addition, the mutant mice sometimes exhibited spontaneously occurring convulsive seizures. Microdialysis measurements revealed that serotonin and dopamine release were markedly reduced in amygdala. These results clearly indicate that PKC-dependent SNAP-25 phosphorylation plays a critical role in the regulation of emotional behavior as well as the suppression of epileptic seizures, and the lack of enhancement of monoamine release is one of the possible mechanisms underlying these defects.
Article
PLOS ONE. 6(9):e25158 (2011)
journal article
PUBLIC LIBRARY SCIENCE
2011-09-20
application/pdf
PLOS ONE
9
6
1932-6203
https://soar-ir.repo.nii.ac.jp/record/12409/files/Single_Amino_Acid_Mutation_SNAP-25.pdf
eng
21949876
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?CMD=search&DB=pubmed&term=21949876
10.1371/journal.pone.0025158
https://doi.org/10.1371/journal.pone.0025158
Copyright © 2011 Kataoka et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.