Ataxin 10 induces neuritogenesis via interaction with G-protein β2 subunit
✍ Scribed by Masaaki Waragai; Shinichiro Nagamitsu; Weidong Xu; Yu Jiang Li; Xi Lin; Tetsuo Ashizawa
- Book ID
- 102386309
- Publisher
- John Wiley and Sons
- Year
- 2006
- Tongue
- English
- Weight
- 417 KB
- Volume
- 83
- Category
- Article
- ISSN
- 0360-4012
No coin nor oath required. For personal study only.
✦ Synopsis
Abstract
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. © 2006 Wiley‐Liss, Inc.