Lysophosphatidic Acid and Thrombin Receptors Require Both Gα_<12> and Gα_<13> to Regulate Axonal Morphology in Hippocampal Neurons(Molecular and Cell Biology)

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The Gα subunits of the G_<12> family of heterotrimeric guanine nucleotide-binding proteins (G proteins), defined by Gα_<12> and Gα_<13>, have many cellular functions in common, including stimulation of stress fiber formation and focal adhesion assembly via the small GTPase RhoA activation. We and others previously showed that Gα_<12> and Gα_<13> mediate neurite retraction in neuronal cell lines, but their roles in primary cultured neurons have not been adequately understood. Here, we found that expression of constitutively active mutants of Gα_<12> or Gα_<13> caused growth cone collapse dependent on Rho-kinase activity in hippocampal neurons. The stimulation of thrombin and lysophosphatidic acid (LPA) receptors, which have been thought to selectively couple to Gα_<12> and Gα_<13>, respectively, caused growth cone collapse and suppressed axon branching dependent on Rho-kinase activity in hippocampal neurons. Thrombin- and LPA-induced growth cone collapse was suppressed by both single knockdown of Gα_<12> and Gα_<13> with short hairpin RNAs and this suppression was augmented by double knockdown of both Gα_<12> and Gα_<13>. These results suggest that thrombin and LPA receptors couple to both Gα_<12> and Gα_<13> for growth cone collapse.
公益社団法人日本薬学会の論文
2008-12-01