Autonomous and nonautonomous regulation of Wnt-mediated neuronal polarity by the C. elegans Ror kinase CAM-1

Dev Biol. 2015 Aug 1;404(1):55-65. doi: 10.1016/j.ydbio.2015.04.015. Epub 2015 Apr 24.

Abstract

Wnts are a conserved family of secreted glycoproteins that regulate various developmental processes in metazoans. Three of the five Caenorhabditis elegans Wnts, CWN-1, CWN-2 and EGL-20, and the sole Wnt receptor of the Ror kinase family, CAM-1, are known to regulate the anterior polarization of the mechanosensory neuron ALM. Here we show that CAM-1 and the Frizzled receptor MOM-5 act in parallel pathways to control ALM polarity. We also show that CAM-1 has two functions in this process: an autonomous signaling function that promotes anterior polarization and a nonautonomous Wnt-antagonistic function that inhibits anterior polarization. These antagonistic activities can account for the weak ALM phenotypes displayed by cam-1 mutants. Our observations suggest that CAM-1 could function as a Wnt receptor in many developmental processes, but the analysis of cam-1 mutants may fail to reveal CAM-1's role as a receptor in these processes because of its Wnt-antagonistic activity. In this model, loss of CAM-1 results in increased levels of Wnts that act through other Wnt receptors, masking CAM-1's autonomous role as a Wnt receptor.

Keywords: C. elegans; CAM-1; Neuronal polarity; Ror kinase.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Caenorhabditis elegans / cytology*
  • Caenorhabditis elegans / metabolism
  • Caenorhabditis elegans Proteins / metabolism*
  • Cell Polarity
  • Membrane Proteins / metabolism*
  • Neurons / cytology*
  • Neurons / metabolism
  • Receptor Tyrosine Kinase-like Orphan Receptors / metabolism*
  • Wnt Signaling Pathway*

Substances

  • Caenorhabditis elegans Proteins
  • Membrane Proteins
  • Mom-5 protein, C elegans
  • CAM-1 protein, C elegans
  • Receptor Tyrosine Kinase-like Orphan Receptors