The α‐subunit of the trimeric GTP ase 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
• 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 Rap1 GTP ase activating protein (Rap1 GAP ) 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 Rap1 GAP . However, we found higher amounts of active Rap1‐ GTP in brains of Go2α deficient mutants, indicating that Go2α may increase Rap1 GAP activity, thereby effecting the Rap1 activation/deactivation cycle. Rap1 has been shown to be involved in neurite outgrowth and given a Rap1 GAP ‐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.