A Single Amino Acid Mutation in SNAP-25 Induces Anxiety-related Behavior in Mouse

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2011 Sep 28

PMID 21949876

Citations 29

Authors

Masakazu Kataoka

Saori Yamamori

Eiji Suzuki

Shigeru Watanabe

Taku Sato

Hitoshi Miyaoka

Sadahiro Azuma

Shiro Ikegami

Reiko Kuwahara

Rika Suzuki-Migishima

Yohko Nakahara

Itsuko Nihonmatsu

Kaoru Inokuchi

Yuko Katoh-Fukui

Minesuke Yokoyama

Masami Takahashi

Affiliations

Soon will be listed here.

Abstract

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.

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