The ENU-3 protein family members function in the Wnt pathway parallel to UNC-6/Netrin to promote motor neuron axon outgrowth in C. elegans

Dev Biol. 2017 Oct 1;430(1):249-261. doi: 10.1016/j.ydbio.2017.06.036. Epub 2017 Jul 8.


The axons of the DA and DB classes of motor neurons fail to reach the dorsal cord in the absence of the guidance cue UNC-6/Netrin or its receptor UNC-5 in C. elegans. However, the axonal processes usually exit their cell bodies in the ventral cord in the absence of both molecules. Strains lacking functional versions of UNC-6 or UNC-5 have a low level of DA and DB motor neuron axon outgrowth defects. We found that mutations in the genes for all six of the ENU-3 proteins function to enhance the outgrowth defects of the DA and DB axons in strains lacking either UNC-6 or UNC-5. A mutation in the gene for the MIG-14/Wntless protein also enhances defects in a strain lacking either UNC-5 or UNC-6, suggesting that the ENU-3 and Wnt pathways function parallel to the Netrin pathway in directing motor neuron axon outgrowth. Our evidence suggests that the ENU-3 proteins are novel members of the Wnt pathway in nematodes. Five of the six members of the ENU-3 family are predicted to be single-pass trans-membrane proteins. The expression pattern of ENU-3.1 was consistent with plasma membrane localization. One family member, ENU-3.6, lacks the predicted signal peptide and the membrane-spanning domain. In HeLa cells ENU-3.6 had a cytoplasmic localization and caused actin dependent processes to appear. We conclude that the ENU-3 family proteins function in a pathway parallel to the UNC-6/Netrin pathway for motor neuron axon outgrowth, most likely in the Wnt pathway.

Keywords: ENU-3 protein family; Motor neuron axon outgrowth; UNC-40/DCC; UNC-6/Netrin, UNC-5; Wnt pathway.

MeSH terms

  • Animals
  • Axons / metabolism*
  • Caenorhabditis elegans / metabolism*
  • Caenorhabditis elegans Proteins / metabolism*
  • Cell Body / metabolism
  • Cell Nucleus / metabolism
  • Endoplasmic Reticulum / metabolism
  • Green Fluorescent Proteins / metabolism
  • HeLa Cells
  • Humans
  • Membrane Proteins / metabolism*
  • Motor Neurons / metabolism*
  • Nerve Tissue Proteins / metabolism*
  • Netrins
  • Neuronal Outgrowth*
  • Wnt Signaling Pathway*


  • Caenorhabditis elegans Proteins
  • Membrane Proteins
  • Nerve Tissue Proteins
  • Netrins
  • UNC-6 protein, C elegans
  • enu-3 protein, C elegans
  • Green Fluorescent Proteins

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