Cytoskeletal Regulation by AUTS2 in Neuronal Migration and Neuritogenesis

Kei Hori, Taku Nagai, Wei Shan, Asami Sakamoto, Shinichiro Taya, Ryoya Hashimoto, Takashi Hayashi, Manabu Abe, Maya Yamazaki, Keiko Nakao, Tomoki Nishioka, Kenji Sakimura, Kiyofumi Yamada, Kozo Kaibuchi, Mikio Hoshino

研究成果: Article査読

57 被引用数 (Scopus)

抄録

Mutations in the Autism susceptibility candidate 2 gene (AUTS2), whose protein is believed to act in neuronal cell nuclei, have been associated with multiple psychiatric illnesses, including autism spectrum disorders, intellectual disability, and schizophrenia. Here we show that cytoplasmic AUTS2 is involved inthe regulation of the cytoskeleton and neural development. Immunohistochemistry and fractionation studies show that AUTS2 localizes not only in nuclei, but also in the cytoplasm, including in the growth cones in the developing brain. AUTS2 activates Rac1 to induce lamellipodia but downregulates Cdc42 to suppress filopodia. Our loss-of-function and rescue experiments show that a cytoplasmic AUTS2-Rac1 pathway is involved in cortical neuronal migration and neuritogenesis in the developing brain. These findings suggest that cytoplasmic AUTS2 acts as a regulator of Rho family GTPases to contribute to brain development and give insight into the pathology of human psychiatric disorders with AUTS2 mutations.

本文言語English
ページ(範囲)2166-2179
ページ数14
ジャーナルCell Reports
9
6
DOI
出版ステータスPublished - 24-12-2014
外部発表はい

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

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