THE ANALYSIS OF THE WNT-RYK SIGNALING PATHWAY IN C. ELEGANS

Abstract

Wnt signaling is well known to regulate various cellular processes during development. Wnt ligands can bind to Fz, Ryk or Ror receptors. In this study, we focused on Wnt-Ryk signaling. Ryk is a single-pass transmembrane receptor, which consists of an extracellular domain (ECD), a transmembrane region (TM) and the intracellular domain (ICD). In C. elegans, lin-18 encodes the Ryk ortholog. We showed that expression of LIN-18ECD-TM is sufficient to rescue the lin-18 loss-of-function phenotype, consistent with previous finding. In contrast, overexpression of LIN-18ICD enhanced the lin-18 loss-of-function phenotype. Like mammalian RykICD, LIN-18ICD tends to localize to the nucleus. We found that the CAM-1/Ror signaling pathway and PAR-5/14-3-3 proteins may regulate LIN-18ICD nuclear localization. In addition, we also studied the role of lipid modification in Wnt signaling. We found that LIN-17/Fz and CAM-1/Ror signaling, but not LIN-18/Ryk signaling, require Porcupine mediated lipid modification of Wnt ligands.