title: A single amino acid mutation in SNAP-25 induces anxiety-related behavior in mouse.
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.
authors.affiliation: Department of Environmental Science and Technology, Faculty of Engineering, Shinshu University, Nagano-shi, Nagano, Japan.
authors.forename: Masakazu
authors.initials: M
authors.lastname: Kataoka
authors.forename: Saori
authors.initials: S
authors.lastname: Yamamori
authors.forename: Eiji
authors.initials: E
authors.lastname: Suzuki
authors.forename: Shigeru
authors.initials: S
authors.lastname: Watanabe
authors.forename: Taku
authors.initials: T
authors.lastname: Sato
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Miyaoka
authors.forename: Sadahiro
authors.initials: S
authors.lastname: Azuma
authors.forename: Shiro
authors.initials: S
authors.lastname: Ikegami
authors.forename: Reiko
authors.initials: R
authors.lastname: Kuwahara
authors.forename: Rika
authors.initials: R
authors.lastname: Suzuki-Migishima
authors.forename: Yohko
authors.initials: Y
authors.lastname: Nakahara
authors.forename: Itsuko
authors.initials: I
authors.lastname: Nihonmatsu
authors.forename: Kaoru
authors.initials: K
authors.lastname: Inokuchi
authors.forename: Yuko
authors.initials: Y
authors.lastname: Katoh-Fukui
authors.forename: Minesuke
authors.initials: M
authors.lastname: Yokoyama
authors.forename: Masami
authors.initials: M
authors.lastname: Takahashi
mesh_terms: D019943:Amino Acid Substitution; D000818:Animals; D001007:Anxiety / Q000209:etiology* / Q000523:psychology; D001522:Behavior, Animal; D015152:Blotting, Northern; D015153:Blotting, Western; D002462:Cell Membrane / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009154:Mutation / Q000235:genetics*; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism*; D022142:Secretory Vesicles / Q000378:metabolism; D050825:Synaptosomal-Associated Protein 25 / Q000502:physiology*
chemical_list: C494209:Snap25 protein, mouse; D050825:Synaptosomal-Associated Protein 25; D011493:Protein Kinase C; D004298:Dopamine