Myosin X regulates netrin receptors and functions in axonal path-finding |
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Authors: | Zhu Xiao-Juan Wang Cheng-Zhong Dai Peng-Gao Xie Yi Song Ning-Ning Liu Yu Du Quan-Sheng Mei Lin Ding Yu-Qiang Xiong Wen-Cheng |
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Institution: | Program of Developmental Neurobiology, IMMAG and Department of Neurology, Medical College of Georgia, Augusta, GA 30912, USA. |
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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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