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

Authors

  • Jens Baron,

    1. Center for Anatomy, Institute for Integrative Neuroanatomy, Functional Cell Biology, Charité-Universitätsmedizin Berlin, Germany
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    • Both authors contributed equally to the article.
  • Christian Blex,

    1. Center for Anatomy, Institute for Integrative Neuroanatomy, Functional Cell Biology, Charité-Universitätsmedizin Berlin, Germany
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    • Both authors contributed equally to the article.
  • Astrid Rohrbeck,

    1. Institute of Toxicology, Hannover Medical School (MHH), Germany
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  • Sivarama Krishna Rachakonda,

    1. Center for Anatomy, Institute for Integrative Neuroanatomy, Functional Cell Biology, Charité-Universitätsmedizin Berlin, Germany
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  • Lutz Birnbaumer,

    1. Laboratory of Neurobiology, Division of Intramural Research, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA
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  • Gudrun Ahnert-Hilger,

    Corresponding author
    • Center for Anatomy, Institute for Integrative Neuroanatomy, Functional Cell Biology, Charité-Universitätsmedizin Berlin, Germany
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  • Irene Brunk

    Corresponding author
    • Center for Anatomy, Institute for Integrative Neuroanatomy, Functional Cell Biology, Charité-Universitätsmedizin Berlin, Germany
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Address correspondence and reprint requests to Irene Brunk or Gudrun Ahnert-Hilger, Institute for Integrative Neuroanatomy, Philippstr. 12, 10115 Berlin, Germany.

E-mails: irene.brunk@charite.de; gudrun.ahnert@charite.de

Abstract

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.

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