Myosin X regulates netrin receptors and functions in axonal path-finding.
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.
Zhu
Xiao-Juan
XJ
Program of Developmental Neurobiology, IMMAG and Department of Neurology, Medical College of Georgia, Augusta, GA 30912, USA.
Wang
Cheng-Zhong
CZ
Dai
Peng-Gao
PG
Xie
Yi
Y
Song
Ning-Ning
NN
Liu
Yu
Y
Du
Quan-Sheng
QS
Mei
Lin
L
Ding
Yu-Qiang
YQ
Xiong
Wen-Cheng
WC
D000818:Animals; D001369:Axons / Q000502:physiology*; D019556:COS Cells; D002460:Cell Line; D002642:Chick Embryo; D002522:Chlorocebus aethiops; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D035683:MicroRNAs / Q000494:pharmacology; D008969:Molecular Sequence Data; D009218:Myosins / Q000187:drug effects / Q000378:metabolism*; D009414:Nerve Growth Factors / Q000378:metabolism* / Q000494:pharmacology; D000075386:Netrin Receptors; D000075388:Netrin-1; D051381:Rats; D011956:Receptors, Cell Surface / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000378:metabolism* / Q000494:pharmacology
C498718:MYO10 protein, human; D008565:Membrane Proteins; D035683:MicroRNAs; C409064:Myo10 protein, mouse; C000617351:NTN1 protein, human; D009414:Nerve Growth Factors; D000075386:Netrin Receptors; C000617353:Ntn1 protein, mouse; C000617354:Ntn1 protein, rat; D011956:Receptors, Cell Surface; D025521:Tumor Suppressor Proteins; C091279:neogenin; D000075388:Netrin-1; D009218:Myosins