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Gα 12 and Gα 13 Inhibit Ca 2+ ‐Dependent Exocytosis Through Rho/Rho‐Associated Kinase‐Dependent Pathway
Author(s) -
Yamaguchi Yoshiaki,
Katoh Hironori,
Yasui Hidekazu,
Aoki Junko,
Nakamura Kazuhiro,
Negishi Manabu
Publication year - 2000
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2000.0750708.x
Subject(s) - heterotrimeric g protein , ionomycin , rhoa , exocytosis , g protein , microbiology and biotechnology , gtpgammas , signal transduction , protein kinase c , biology , chemistry , intracellular , biochemistry , secretion
The release of neurotransmitters is known to be regulated by activation of heterotrimeric G protein‐coupled receptors, although precise mechanisms have not yet been elucidated. To assess the role of the G 12 family of heterotrimeric G proteins in the regulation of neurotransmitter release, we established PC12 cell lines that expressed constitutively active Gα 12 or Gα 13 using an isopropyl‐β‐ d ‐thiogalactoside‐inducible expression system. In the cells, expression of constitutively active Gα 12 or Gα 13 inhibited the high K + ‐evoked [ 3 H]dopamine release without any effect on the high K + ‐induced increase in intracellular Ca 2+ concentration. A Ca 2+ ionophore ionomycin‐induced [ 3 H]dopamine release was also inhibited by the expression of active Gα 12 or Gα 13 . These inhibitory effects of Gα 12 and Gα 13 on [ 3 H]dopamine release were mimicked by the expression of constitutively active RhoA. In addition, Y‐27632, and inhibitor of Rho‐associated kinase, a downstream Rho effector, completely abolished the inhibition of [ 3 H]dopamine release by Gα 12 , Gα 13 , and RhoA. These results indicate that Ca 2+ ‐dependent exocytosis is regulated by Gα 12 and Gα 13 through a Rho/Rho‐associated kinase‐dependent pathway.