Ataxin 10 induces neuritogenesis via interaction with G-protein β2 subunit

Masaaki Waragai, Shinichiro Nagamitsu, Weidong Xu, Jiang Li Yu, Xi Lin, Tetsuo Ashizawa

Research output: Contribution to journalArticlepeer-review

31 Scopus citations


Spinocerebellar ataxia type 10 (SCA10) is a dominantly inherited disorder caused by an intronic ATTCT pentanucleotide repeat expansion. The ATXN10 gene encodes a novel protein, ataxin 10, known previously as E46L, which is widely expressed in the brain. Ataxin 10 deficiency has been shown recently to cause increased apoptosis in primary cerebellar cultures, thus implicated in SCA10 pathogenesis. The biologic functions of ataxin 10 remain largely unknown. By using yeast-two-hybrid screening of a human brain cDNA library, we identified the G-protein β2 subunit (Gβ2) as an ataxin 10 binding partner, and the interaction was confirmed by coimmunoprecipitation and colocalization in mammalian cells in culture. Overexpression of ataxin 10 in PC12 cells induced neurite extension and enhanced neuronal differentiation induced by nerve growth factor (NGF). Moreover, coexpression of ataxin 10 and Gβ2 potently activated the Ras-MAP kinase-Elk-1 cascade. Dominant negative Ras or inhibitor of MEK-1/2 (U0126) aborted this activation, and blocked morphologic changes, whereas inhibition of TrkA receptor by K252a had no effects. Our data suggest that the ataxin 10-Gβ2 interaction represents a novel mechanism for inducing neuritogenesis in PC12 cells by activating the Ras-MAP kinase-Elk-1 cascade.

Original languageEnglish (US)
Pages (from-to)1170-1178
Number of pages9
JournalJournal of Neuroscience Research
Issue number7
StatePublished - May 15 2006


  • Gβ2
  • MAP kinase
  • Neuronal differentiation
  • Ras
  • Spinocerebellar ataxia type 10

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience


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