Autonomous and nonautonomous regulation of Wnt-mediated neuronal polarity by the C. elegans Ror kinase CAM-1.
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.
Department of Molecular and Cell Biology, University of California, Berkelry, CA 94720, United States.
Shih-Chieh Jason
SC
Chien
Department of Molecular and Cell Biology, University of California, Berkelry, CA 94720, United States.
Mark
M
Gurling
Department of Medical and Molecular Genetics, Indiana University Medical Sciences, Indiana University, Bloomington, IN 47405, United States.
Changsung
C
Kim
Department of Medical and Molecular Genetics, Indiana University Medical Sciences, Indiana University, Bloomington, IN 47405, United States.
Teresa
T
Craft
Department of Medical and Molecular Genetics, Indiana University Medical Sciences, Indiana University, Bloomington, IN 47405, United States.
Wayne
W
Forrester
Department of Molecular and Cell Biology, University of California, Berkelry, CA 94720, United States; Helen Wills Neuroscience Institute, University of California, Berkeley, CA 94720, United States. Electronic address: garriga@berkeley.edu.
Gian
G
Garriga
D000818:Animals; D030801:Animals, Genetically Modified; D017173:Caenorhabditis elegans / Q000166:cytology* / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism*; D016764:Cell Polarity; D008565:Membrane Proteins / Q000378:metabolism*; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D057050:Receptor Tyrosine Kinase-like Orphan Receptors / Q000378:metabolism*; D060449:Wnt Signaling Pathway
D029742:Caenorhabditis elegans Proteins; D008565:Membrane Proteins; C108315:Mom-5 protein, C elegans; C526267:CAM-1 protein, C elegans; D057050:Receptor Tyrosine Kinase-like Orphan Receptors
C. elegans; CAM-1; Neuronal polarity; Ror kinase