Myosin X regulates netrin receptors and functions in axonal path-finding

Xiao Juan Zhu, Cheng Zhong Wang, Peng Gao Dai, Yi Xie, Ning Ning Song, Yu Liu, Quan Sheng Du, Lin Mei, Yu Qiang Ding, Wen Cheng Xiong

Research output: Contribution to journalArticle

106 Scopus citations

Abstract

Netrins regulate axon path-finding during development, but the underlying mechanisms are not well understood. Here, we provide evidence for the involvement of the unconventional myosin X (Myo X) in netrin-1 function. We find that Myo X interacts with the netrin receptor deleted in colorectal cancer (DCC) and neogenin, a DCC-related protein. Expression of Myo X redistributes DCC to the cell periphery or to the tips of neurites, whereas its silencing prevents DCC distribution in neurites. Moreover, expression of DCC, but not neogenin, stimulates Myo X-mediated formation and elongation of filopodia, suggesting that Myo X function may be differentially regulated by DCC and neogenin. The involvement of Myo X in netrin-1 function was further supported by the effects of inhibiting Myo X function in neurons. Cortical explants derived from mouse embryos expressing a motor-less Myo X exhibit reduced neurite outgrowth in response to netrin-1 and chick commissural neurons expressing the motor-less Myo X, or in which Myo X is silenced using microRNA (miRNA), show impaired axon projection in vivo. Taken together, these results identify a novel role for Myo X in regulating netrin-1 function.

Original languageEnglish (US)
Pages (from-to)184-192
Number of pages9
JournalNature Cell Biology
Volume9
Issue number2
DOIs
StatePublished - Feb 1 2007

ASJC Scopus subject areas

  • Cell Biology

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    Zhu, X. J., Wang, C. Z., Dai, P. G., Xie, Y., Song, N. N., Liu, Y., Du, Q. S., Mei, L., Ding, Y. Q., & Xiong, W. C. (2007). Myosin X regulates netrin receptors and functions in axonal path-finding. Nature Cell Biology, 9(2), 184-192. https://doi.org/10.1038/ncb1535