Cytoskeletal Regulation by AUTS2 in Neuronal Migration and Neuritogenesis
| Autor: | Maya Yamazaki, Kenji Sakimura, Wei Shan, Taku Nagai, Ryoya Hashimoto, Keiko Nakao, Kiyofumi Yamada, Kei Hori, Kozo Kaibuchi, Tomoki Nishioka, Takashi Hayashi, Asami Sakamoto, Mikio Hoshino, Manabu Abe, Shinichiro Taya |
|---|---|
| Jazyk: | angličtina |
| Předmět: |
rac1 GTP-Binding Protein
Neurogenesis RAC1 GTPase CDC42 Biology General Biochemistry Genetics and Molecular Biology Mice Cell Movement Animals Humans Pseudopodia Cytoskeleton Growth cone cdc42 GTP-Binding Protein lcsh:QH301-705.5 Cells Cultured Neurons Mice Inbred ICR Neuropeptides Brain Nuclear Proteins Cell biology Actin Cytoskeleton Cytoskeletal Proteins lcsh:Biology (General) Lamellipodium Filopodia Neural development Transcription Factors |
| Zdroj: | Cell Reports, Vol 9, Iss 6, Pp 2166-2179 (2014) |
| ISSN: | 2211-1247 |
| DOI: | 10.1016/j.celrep.2014.11.045 |
| Popis: | Summary 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: | OpenAIRE |
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