The Planar Polarity Protein VANG-1 Antagonizes Wnt Signaling by Promoting Frizzled Endocytosis

• Main Authors: Chun-Wei He, 何俊緯
• Other Authors: Chun-Liang Pan
• Format: Others
• Language: en_US
• Published: 2016
• Online Access: http://ndltd.ncl.edu.tw/handle/16382971475653137153

碩士 === 國立臺灣大學 === 分子醫學研究所 === 104 === Signaling of neuronal guidance cues through their receptors is tightly regulated both temporally and spatially, allowing the migrating neurons or growth cones to respond promptly to changing guidance cues in the environments. The conserved Wnt family of secreted glycoproteins control neuronal migration and axon guidance through Frizzled receptors. We report here that VANG-1/Vangl2/Strabismus, a membrane protein important for planar tissue polarity, antagonized Frizzled functions in C. elegans neuronal migration. In the absence of Wnt-Frizzled signaling, descendants of the QL neuroblast mismigrated towards the anterior, and those of the QR neuroblast, as well as the HSN motor neurons, stopped prematurely in their anterior migration. Mutations in vang-1 significantly rescued these phenotypes, and cell-specific overexpression of VANG-1 phenocopied Wnt and Frizzled mutants for neuronal migration defects. Our genetic analysis suggested that VANG-1 specifically targeted the Frizzled receptors, but not the Wnt ligands or components downstream of the Frizzleds. This conclusion was further substantiated by the following observations: First, VANG-1 formed protein complexes with the Frizzleds MIG-1 and MOM-5. Second, VANG-1 facilitated Frizzled localization to the cytosol, and Frizzleds tended to accumulate on the neuronal membrane in the vang-1 mutant. We propose that VANG-1 promotes Frizzled endocytosis and prevents prolonged or excessive Wnt signaling to achieve proper regulation of neuroblast migration in C. elegans.