Cytoskeletal Regulation by AUTS2 in Neuronal Migration and Neuritogenesis
| Autor: | 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 |
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| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: | |
| Zdroj: | Cell Reports, Vol 9, Iss 6, Pp 2166-2179 (2014) |
| Druh dokumentu: | article |
| ISSN: | 2211-1247 42077389 |
| DOI: | 10.1016/j.celrep.2014.11.045 |
| Popis: | 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 in the 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. |
| Databáze: | Directory of Open Access Journals |
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