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Semaphorin 3A induces CaV2.3 channel-dependent conversion of axons to dendrites

Nature Cell Biology volume 13, pages 676–685 (2011)Cite this article

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Abstract

Polarized neurites (axons and dendrites) form the functional circuitry of the nervous system. Secreted guidance cues often control the polarity of neuron migration and neurite outgrowth by regulating ion channels. Here, we show that secreted semaphorin 3A (Sema3A) induces the neurite identity of Xenopus spinal commissural interneurons (xSCINs) by activating CaV2.3 channels (CaV2.3). Sema3A treatment converted the identity of axons of cultured xSCINs to that of dendrites by recruiting functional CaV2.3. Inhibition of Sema3A signalling prevented both the expression of CaV2.3 and acquisition of the dendrite identity, and inhibition of CaV2.3 function resulted in multiple axon-like neurites of xSCINs in the spinal cord. Furthermore, Sema3A-triggered cGMP production and PKG activity induced, respectively, the expression of functional CaV2.3 and the dendrite identity. These results reveal a mechanism by which a guidance cue controls the identity of neurites during nervous system development.

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Figure 1: Sema3A converts the identity of axons to dendrites by CaV2.3 activity.
Figure 2: Sema3A increases growth-cone CaV2.3 currents.
Figure 3: Sema3A is required for CaV2.3 expression in Xenopus spinal cords.
Figure 4: Sema3A signalling is required for acquisition of the dendrite identity of putative xSCINs in vivo.
Figure 5: CaV2.3 function is required for the dendrite identity of xSCINs in vivo.
Figure 6: CaV2.3 activity suppresses the acquisition of the axon identity of xSCINs in vivo.
Figure 7: Sema3A-induced cGMP causes recruitment and expression of CaV2.3 and PKG is required as a co-activator for acquisition of the dendrite identity.
Figure 8: Model depicting Sema3A-induced acquisition of the dendrite identity.

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Acknowledgements

We thank Drs W. R. Jelinek, N. J. Cowan, M. E. Rice, M-M. Poo, D. Ginty and A. L. Kolodkin for critical comments on the manuscript, S. M. Strittmatter for the NP-1(0111) and L. I. Binder and G. Tian for technical assistance. This work was supported by grants from NIH/NINDS (NS042823 and CRCNS Program, NS064671, K.H.), MEXT (Grants-in-Aid and Targeted Protein Research Project, Y.G.) and RIKEN (Computational Science Research Program, S.I.).

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Author notes

  1. Chae-Seok Lim

    Present address: Present address: Department of Pharmacology, University of Virginia School of Medicine, Charlottesville, Virginia 22908, USA,

  2. Makoto Nishiyama, Kazunobu Togashi and Melanie J. von Schimmelmann: These authors contributed equally to this work

Authors and Affiliations

  1. Department of Biochemistry, New York University School of Medicine, New York, New York 10016-6402, USA

    Makoto Nishiyama, Kazunobu Togashi, Melanie J. von Schimmelmann, Chae-Seok Lim & Kyonsoo Hong

  2. Department of Systems Science, Graduate School of Informatics, Kyoto University, Uji 611-0011, Japan

    Shin-ichi Maeda & Shin Ishii

  3. Department of Molecular Pharmacology and Neurobiology, Yokohama City University School of Medicine, Yokohama 236-0004, Japan

    Naoya Yamashita & Yoshio Goshima

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Contributions

M.N., K.T., M.J.v.S. and K.H. designed and carried out experiments and analysed the data; C-S.L. helped with immunocytochemisty; N.Y. and Y.G. provided proteins; M.N., K.T., S-i.M. and S.I. carried out or supervised in vivo imaging analyses; M.N. and K.H. supervised the project and wrote the manuscript.

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Correspondence to Makoto Nishiyama or Kyonsoo Hong.

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Nishiyama, M., Togashi, K., von Schimmelmann, M. et al. Semaphorin 3A induces CaV2.3 channel-dependent conversion of axons to dendrites. Nat Cell Biol 13, 676–685 (2011). https://doi.org/10.1038/ncb2255

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