C. elegans LIN-18 is a Ryk ortholog and functions in parallel to LIN-17/Frizzled in Wnt signaling.
Wnt proteins are intercellular signals that regulate various aspects of animal development. In Caenorhabditis elegans, mutations in lin-17, a Frizzled-class Wnt receptor, and in lin-18 affect cell fate patterning in the P7.p vulval lineage. We found that lin-18 encodes a member of the Ryk/Derailed family of tyrosine kinase-related receptors, recently found to function as Wnt receptors. Members of this family have nonactive kinase domains. The LIN-18 kinase domain is dispensable for LIN-18 function, while the Wnt binding WIF domain is required. We also found that Wnt proteins LIN-44, MOM-2, and CWN-2 redundantly regulate P7.p patterning. Genetic interactions indicate that LIN-17 and LIN-18 function independently of each other in parallel pathways, and different ligands display different receptor specificities. Thus, two independent Wnt signaling pathways, one employing a Ryk receptor and the other a Frizzled receptor, function in parallel to regulate cell fate patterning in the C. elegans vulva.
Inoue
Takao
T
Division of Biology, California Institute of Technology, Pasadena 91125, USA.
Oz
Helieh S
HS
Wiland
Debra
D
Gharib
Shahla
S
Deshpande
Rashmi
R
Hill
Russell J
RJ
Katz
Wendy S
WS
Sternberg
Paul W
PW
D000595:Amino Acid Sequence / Q000235:genetics; D000818:Animals; D001483:Base Sequence / Q000235:genetics; D001665:Binding Sites / Q000502:physiology; D019521:Body Patterning / Q000235:genetics; D017173:Caenorhabditis elegans / Q000166:cytology / Q000235:genetics / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D002454:Cell Differentiation / Q000235:genetics; D018076:DNA, Complementary / Q000032:analysis / Q000235:genetics; D005260:Female; D051157:Frizzled Receptors; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D006023:Glycoproteins / Q000378:metabolism; D008969:Molecular Sequence Data; D011485:Protein Binding / Q000502:physiology; D017434:Protein Structure, Tertiary / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism*; D017981:Receptors, Neurotransmitter / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D051153:Wnt Proteins
D029742:Caenorhabditis elegans Proteins; D018076:DNA, Complementary; C489740:FZD1 protein, human; D051157:Frizzled Receptors; D006023:Glycoproteins; C101684:LIN-17 protein, C elegans; C095991:LIN-44 protein, C elegans; D011518:Proto-Oncogene Proteins; D043562:Receptors, G-Protein-Coupled; D017981:Receptors, Neurotransmitter; D051153:Wnt Proteins; C492691:LIN-18 protein, C elegans; C080836:RYK protein, human; D020794:Receptor Protein-Tyrosine Kinases