Discovery of long-range inhibitory signaling to ensure single axon formation

• 本田, 直樹

• Wu, Mengya

• Nakamuta, Shinichi

• Naoki, Honda

• Ishizawa, Naruki

• Namba, Takashi

• Watanabe, Takashi

• Xu, Chundi

• Hamaguchi, Tomonari

• Yura, Yoshimitsu

• Amano, Mutsuki

• Hahn, Klaus M.

• Kaibuchi, Kozo

抄録

A long-standing question in neurodevelopment is how neurons develop a single axon and multiple dendrites from common immature neurites. Long-range inhibitory signaling from the growing axon is hypothesized to prevent outgrowth of other immature neurites and to differentiate them into dendrites, but the existence and nature of this inhibitory signaling remains unknown. Here, we demonstrate that axonal growth triggered by neurotrophin-3 remotely inhibits neurite outgrowth through long-range Ca[2+] waves, which are delivered from the growing axon to the cell body. These Ca[2+] waves increase RhoA activity in the cell body through calcium/calmodulin-dependent protein kinase I. Optogenetic control of Rho-kinase combined with computational modeling reveals that active Rho-kinase diffuses to growing other immature neurites and inhibits their outgrowth. Mechanistically, calmodulin-dependent protein kinase I phosphorylates a RhoA-specific GEF, GEF-H1, whose phosphorylation enhances its GEF activity. Thus, our results reveal that long-range inhibitory signaling mediated by Ca[2+] wave is responsible for neuronal polarization.

収録刊行物

• Nature Communications

  Nature Communications 8 1-, 2017-06-26

  Springer Nature

キーワード

• Cellular neuroscience
• Neuronal development

詳細情報

• CRID: 1050845760779463424
• NII論文ID: 120006325188
• ISSN: 20411723
• DOI: 10.1038/s41467-017-00044-2
• HANDLE: 2433/226512
• Web Site: https://www.nature.com/articles/s41467-017-00044-2.pdf
• Web Site: https://www.nature.com/articles/s41467-017-00044-2
• 本文言語コード: en
• 資料種別: journal article
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