TY - JOUR
T1 - A single amino acid mutation in SNAP-25 induces anxiety-related behavior in mouse
AU - Kataoka, Masakazu
AU - Yamamori, Saori
AU - Suzuki, Eiji
AU - Watanabe, Shigeru
AU - Sato, Taku
AU - Miyaoka, Hitoshi
AU - Azuma, Sadahiro
AU - Ikegami, Shiro
AU - Kuwahara, Reiko
AU - Suzuki-Migishima, Rika
AU - Nakahara, Yohko
AU - Nihonmatsu, Itsuko
AU - Inokuchi, Kaoru
AU - Katoh-Fukui, Yuko
AU - Yokoyama, Minesuke
AU - Takahashi, Masami
PY - 2011/9/20
Y1 - 2011/9/20
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=80052944672&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0025158
DO - 10.1371/journal.pone.0025158
M3 - 学術論文
C2 - 21949876
AN - SCOPUS:80052944672
SN - 1932-6203
VL - 6
JO - PLoS ONE
JF - PLoS ONE
IS - 9
M1 - e25158
ER -