抄録
Regulation of neurotransmitter release by tomosyn phosphorylation. Sumiko Mochida1, Takeshi Baba2, Toshiaki Sakisaka2, and Yoshimi Takai2. 1Depatment of Physiology, Tokyo Medical University, Shinjuku 160-8402, Japan, and 2Department of Molecular Biology and Biochemistry, Osaka University Graduate School of Medicine/Faculty of Medicine, Suita 565-0871, Japan.PKA phosphorylation of tomosyn, a SNARE regulatory protein, significantly decreased its binding to syntaxin-1 in vitro, and cAMP stimulation increased the phosphorylation of tomosyn and decreased tomosyn binding to syntaxin-1, resulting in enhanced SNARE complex formation. Overexpression of tomosyn in cultured superior cervical ganglion neurons inhibited neurotransmitter release which could be rescued by the introduction of cAMP into the presynaptic neuron. Expression of tomosyn S724A, a PKA unphosphorylated mutant, or knock-down of tomosyn by siRNA introduction also decreased neurotransmitter release, but was not rescued by cAMP. Under high frequency stimulation, expression of tomosyn S724A and S724D, a PKA phosphorylated mimic mutant, increased the EPSP failure rate and asynchronous EPSPs. These results indicate that tomosyn is a physiologically significant PKA target that controls neurotransmitter release through the regulation of SNARE complex formation. [J Physiol Sci. 2006;56 Suppl:S85]
