1994 Fiscal Year Final Research Report Summary
Roles of G-proteins and cytoskeletal porteins in transmitter release.
| Project/Area Number |
05680683
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Neurochemistry/Neuropharmacology
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| Research Institution | Sophia University |
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Principal Investigator |
KUMAKURA Konosuke Sohia University, Faculty of Science and Technology, Professor, 理工学部, 教授 (70129790)
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| Co-Investigator(Kenkyū-buntansha) |
IMAIZUMI Mica Sophia University, Life Science Institute, Assistant, 生命科学研究所, 助手 (40201941)
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| Project Period (FY) |
1993 – 1994
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| Keywords | Mechanism of Exocytosis / Transmitter Release / GTP-Binding Proteins / Myosin Light Chain Kinase / Ca^<2+>-Dependent Release / ATP-Dependent Priming / Mastoparan / Cytoskeletal Proteins |
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| Research Abstract |
The aim of this research project is to clarify the roles of GTP-binding proteins and cytoskeletal proteins in the mechanism of transmitter release.Previously we have suggested that Go, one of heterotrimeric GTP-binding proteins, negatively regulates Ca^<2+>-dependent release of catecholamine in permeabilized chromaffin cells.We also have suggested a possible involvement of myosin light chain kinase in the mechanism of Ca^<2+>-dependent exocytosis.In the project, we attempted to elucidate the mechanism whereby Ca^<2+>-dependent release is regulated by Go, and by myosin light chain kinase in permeabilized chromaffin cells.We have obtained the following results.
1.By use of mastoparan, a peptide known to activate directly GTP-binding proteins, and by use of anti-Go antibodies, we found that the negative regulation by Go is on the process of ATP-dependent priming of exocytosis.This inhibitory Go was suggested to be activated by GAP43, and activation of protein kinase C seemed to stimulate Ca^<2+>-dependent release by abolishing the action of GAP43 on Go.
2.We found that myosin light chain kinase is essential for ATP-dependent priming of exocytosis, by use of specific inhibitors of myosin light chain kinase, wortmannin and SM-1.Histochemical studies suggested that the inhibition of myosin light chain kinase inhibits reorganization of cortical F-actin, and thus suggested an important role of cortical F-actin for priming of chromaffin vesicles to the exocytotic site.
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