Lysophosphatidic Acid and Thrombin Receptors Require Both G.ALPHA.12 and G.ALPHA.13 to Regulate Axonal Morphology in Hippocampal Neurons
Year: 2008
Type: article
Abstract: The G alpha subunits of the G(12) family of heterotrimeric guanine nucleotide-binding proteins (G proteins), defined by G alpha(12) and G alpha(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 G alpha(12) and G alpha(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 G alpha(12) or G alpha(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 G alpha(12) and G alpha(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 G alpha(12) and G alpha(13) with short hairpin RNAs and this suppression was augmented by double knockdown of both G alpha(12) and G alpha(13). These results suggest that thrombin and LPA receptors couple to both G alpha(12) and G alpha(13) for growth cone collapse.
DOI: 10.1248/bpb.31.2216
Authors: Junya Yamazaki, Hironori Katoh, Manabu Negishi
Institution: Kyoto University
Language: English
Subfield: Cellular and Molecular Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: bronze
OpenAlex ID: W2028601848