New Aspects of Neurotransmitter Release and Exocytosis: Involvement of Ca^<2+>/Calmodulin-Dependent Phosphorylation of Synapsin I in Insulin Exocytosis
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概要
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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 βe 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 βe or δ2 isoform. These results suggest that activation of CaMKII and the concomitant phosphorylation of synapsin I induce insulin exocytosis from pancreatic β-cells.
- 社団法人 日本薬理学会の論文
- 2003-09-01
著者
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Matsumoto Kazuya
Department Of Genetic Engineering Graduate School Of Biology Oriented Science And Technology Kinki U
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Araki Eiichi
Department Of Metabolic Medicine Faculty Of Medical And Pharmaceutical Sciences Kumamoto University
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Araki Eiichi
Department Of Metabolic Medicine Kumamoto University School Of Medicine
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Miyamoto Eishichi
Department Of Electrical Engineering And Bioscience Graduate School Of Science And Engineering Wased
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Yamamoto Hideyuki
Department Of Molecular Pharmacology Graduate School Of Medical Sciences Kumamoto University
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Yamamoto Hideyuki
Department Of Pharmacology Kumamoto University School Of Medicine
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Matsumoto Kazuya
Department Of Metabolic Medicine Kumamoto University School Of Medicine
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Matsumoto Kazuya
Department Of Applied Chemistry Kanagawa Institute Of Technology
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Araki Eiichi
Department Of Metabolic Medicine Faculty Of Life Sciences Kumamoto University
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Yamamoto Hideyuki
Department Of Biochemistry Graduate School Of Medicine University Of The Ryukyus
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- New Aspects of Neurotransmitter Release and Exocytosis: Involvement of Ca^/Calmodulin-Dependent Phosphorylation of Synapsin I in Insulin Exocytosis
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