New Aspects of Neurotransmitter Release and Exocytosis: Involvement of Ca2+/Calmodulin-Dependent Phosphorylation of Synapsin I in Insulin Exocytosis

Journal of Pharmacological Sciences

Kazuya Matsumoto²  Eishichi Miyamoto¹  Eiichi Araki²  Hideyuki Yamamoto¹ 

[1] Department of Pharmacology, Kumamoto University School of Medicine;Department of Metabolic Medicine, Kumamoto University School of Medicine

关键词: calmodulin;    Ca2+/calmodulin-dependent protein kinase II;    exocytosis;    insulin;    synapsin I;   

DOI  :  10.1254/jphs.93.30

学科分类：药学

来源: Nihon Yakuri Gakkai Henshuubu / Japanese Pharmacological Society

【 摘 要 】

References(28)Cited-By(12)The exocytosis of insulin from pancreatic β-cells is closely related to intracellular elevation of Ca2+. The effects of Ca2+ may be mediated by Ca2+/calmodulin-dependent protein kinase II (CaMKII). Four subunits of CaMKII, termed α, β, γ, and δ, are encoded by distinct genes, and various isoforms of these subunits exist as different splicing variants. In the brain, phosphorylation of synapsin I by the α isoform induces neurotransmitter release. In order to clarify whether phosphorylation of synapsin I by CaMKII was involved in insulin exocytosis, we cloned the isoforms of CaMKII and synapsin I from mouse insulinoma MIN6 cells. We found that β'e and δ2 are the major isoforms of CaMKII and that synapsin Ib is a major isoform of synapsin I in MIN6 cells. It was interesting that δ2 and synapsin Ib were co-localized with insulin secretory granules in the cells. Treatment of MIN6 cells with glucose and tolbutamide rapidly activated CaMKII. Immunoblot analysis with two antibodies against synapsin I phosphorylated by CaMKII demonstrated the increase in phosphorylation of synapsin I by the secretagogues. Furthermore, the secretagogue-induced phosphorylation of synapsin I and insulin secretion were potentiated by transient overexpression of the β'e or δ2 isoform. These results suggest that activation of CaMKII and the concomitant phosphorylation of synapsin I induce insulin exocytosis from pancreatic β-cells.

【 授权许可】

Unknown