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

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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.

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Figure 1: Myo X interaction with DCC and neogenin.
Figure 2: Regulation of DCC distribution in neurons by Myo X.
Figure 3: Distinct regulation by DCC and neogenin of Myo X-mediated filopodium elongation in NLT cells.
Figure 4: Involvement of Myo X in netrin-1-induced cortical neurite outgrowth.
Figure 5: Impaired commissural neuronal axon projections in chicken embryos expressing motor-less Myo X or miRNA.

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Acknowledgements

This study was supported in part by grants from the National Institutes of Health (L.M. and W.C.X.), Muscular Dystrophy Association (L.M.), Philips Morris Research Program (L.M.), and National Nature Science Foundation of China (Y.Q.D. and W.C. X.).

Author information

All authors contributed to the experimental work and/or data analysis. Y.-Q.D. and W.-C.X. contributed to project planning.

Correspondence to Yu-Qiang Ding or Wen-Cheng Xiong.

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The authors declare no competing financial interests.

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