The α‐subunit of the trimeric GTPase Go2 regulates axonal growth

• Published in: Journal of neurochemistry 2013-03, Vol.124 (6), p.782-794
• Main Authors: Baron, Jens, Blex, Christian, Rohrbeck, Astrid, Rachakonda, Sivarama Krishna, Birnbaumer, Lutz, Ahnert‐Hilger, Gudrun, Brunk, Irene
• Format: Article
• Language: English
• Subjects: Animals; axonal growth; Axons - physiology; Cells, Cultured; Enzyme Activation - physiology; Girdin; Go2α; GTP Phosphohydrolases - metabolism; GTP Phosphohydrolases - physiology; GTP-Binding Protein alpha Subunit, Gi2 - physiology; heterotrimeric G‐proteins; Mice; Mice, 129 Strain; Mice, Inbred C57BL; Mice, Knockout; Protein Subunits - physiology; Rap1; Rap1GAP
• ISSN: 0022-3042; 1471-4159
• DOI: 10.1111/jnc.12123

The Goα splice variants Go1α and Go2α are subunits of the most abundant G‐proteins in brain, Go1 and Go2. Only a few interacting partners binding to Go1α have been described so far and splice variant‐specific differences are not known. Using a yeast two‐hybrid screen with constitutively active Go2α as bait, we identified Rap1GTPase activating protein (Rap1GAP) and Girdin as interacting partners of Go2α, which was confirmed by co‐immunoprecipitation. Comparison of subcellular fractions from brains of wild type and Go2α−/− mice revealed no differences in the overall expression level of Girdin or Rap1GAP. However, we found higher amounts of active Rap1‐GTP in brains of Go2α deficient mutants, indicating that Go2α may increase Rap1GAP activity, thereby effecting the Rap1 activation/deactivation cycle. Rap1 has been shown to be involved in neurite outgrowth and given a Rap1GAP‐Go2α interaction, we found that the loss of Go2α affected axonal outgrowth. Axons of cultured cortical and hippocampal neurons prepared from embryonic Go2α−/− mice grew longer and developed more branches than those from wild‐type mice. Taken together, we provide evidence that Go2α regulates axonal outgrowth and branching. Go1α is known to be involved in axonal growth, whereas Go2α had not been investigated in this respect so far. Active Go2α interacts with Rap1GAP. Cerebral Rap1GTP levels and axonal growth and branching are enhanced in Go2α−/− mice, when compared with wild‐type mice. Go2α regulates axonal growth, most likely via Rap1GAP and Rap1.