Letter abstract
Nature Cell Biology 9, 184 - 192 (2007)
Published online: 21 January 2007 | doi:10.1038/ncb1535
Myosin X regulates netrin receptors and functions in axonal path-finding
Xiao-Juan Zhu1,4, Cheng-Zhong Wang2,4, Peng-Gao Dai1,4, Yi Xie3, Ning-Ning Song2, Yu Liu1, Quan-Sheng Du1, Lin Mei1, Yu-Qiang Ding2 & Wen-Cheng Xiong1
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.
- Program of Developmental Neurobiology, IMMAG and Department of Neurology, Medical College of Georgia, Augusta, GA 30912, USA.
- Institute of Neuroscience and Key Laboratory of Neurobiology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
- Department of Pathology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
- These authors contributed equally to this work.
Correspondence to: Yu-Qiang Ding2 e-mail: dingyq@ion.ac.cn
Correspondence to: Wen-Cheng Xiong1 e-mail: wxiong@mcg.edu
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