title: Myosin X regulates netrin receptors and functions in axonal path-finding.
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.
authors.affiliation: Program of Developmental Neurobiology, IMMAG and Department of Neurology, Medical College of Georgia, Augusta, GA 30912, USA.
authors.forename: Xiao-Juan
authors.initials: XJ
authors.lastname: Zhu
authors.forename: Cheng-Zhong
authors.initials: CZ
authors.lastname: Wang
authors.forename: Peng-Gao
authors.initials: PG
authors.lastname: Dai
authors.forename: Yi
authors.initials: Y
authors.lastname: Xie
authors.forename: Ning-Ning
authors.initials: NN
authors.lastname: Song
authors.forename: Yu
authors.initials: Y
authors.lastname: Liu
authors.forename: Quan-Sheng
authors.initials: QS
authors.lastname: Du
authors.forename: Lin
authors.initials: L
authors.lastname: Mei
authors.forename: Yu-Qiang
authors.initials: YQ
authors.lastname: Ding
authors.forename: Wen-Cheng
authors.initials: WC
authors.lastname: Xiong
mesh_terms: 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
chemical_list: 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