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

Nat Cell Biol. 2007 Feb;9(2):184-92. doi: 10.1038/ncb1535. Epub 2007 Jan 21.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Axons / physiology*
  • COS Cells
  • Cell Line
  • Chick Embryo
  • Chlorocebus aethiops
  • Humans
  • Membrane Proteins / metabolism
  • Mice
  • MicroRNAs / pharmacology
  • Molecular Sequence Data
  • Myosins / drug effects
  • Myosins / metabolism*
  • Nerve Growth Factors / metabolism*
  • Nerve Growth Factors / pharmacology
  • Netrin Receptors
  • Netrin-1
  • Rats
  • Receptors, Cell Surface / metabolism*
  • Tumor Suppressor Proteins / metabolism*
  • Tumor Suppressor Proteins / pharmacology


  • MYO10 protein, human
  • Membrane Proteins
  • MicroRNAs
  • Myo10 protein, mouse
  • NTN1 protein, human
  • Nerve Growth Factors
  • Netrin Receptors
  • Ntn1 protein, mouse
  • Ntn1 protein, rat
  • Receptors, Cell Surface
  • Tumor Suppressor Proteins
  • neogenin
  • Netrin-1
  • Myosins

Associated data

  • GENBANK/NP062345