RRC ID 59355
Author He CW, Liao CP, Chen CK, Teulière J, Chen CH, Pan CL.
Title The polarity protein VANG-1 antagonizes Wnt signaling by facilitating Frizzled endocytosis.
Journal Development
Abstract Signaling that instructs the migration of neurons needs to be tightly regulated to ensure precise positioning of neurons and subsequent wiring of the neuronal circuits. Wnt-Frizzled signaling controls neuronal migration in metazoans, in addition to many other aspects of neural development. We show that Caenorhabditis elegans VANG-1, a membrane protein that acts in the planar cell polarity (PCP) pathway, antagonizes Wnt signaling by facilitating endocytosis of the Frizzled receptors. Mutations of vang-1 suppress migration defects of multiple classes of neurons in the Frizzled mutants, and overexpression of vang-1 causes neuronal migration defects similar to those of the Frizzled mutants. Our genetic experiments suggest that VANG-1 facilitates Frizzled endocytosis through β-arrestin2. Co-immunoprecipitation experiments indicate that Frizzled proteins and VANG-1 form a complex, and this physical interaction requires the Frizzled cysteine-rich domain. Our work reveals a novel mechanism mediated by the PCP protein VANG-1 that downregulates Wnt signaling through Frizzled endocytosis.
Volume 145(24)
Published 2018-12-17
DOI 10.1242/dev.168666
PII dev.168666
PMID 30504124
PMC PMC6919297
MeSH Amino Acid Sequence Animals Base Sequence Caenorhabditis elegans / cytology* Caenorhabditis elegans / metabolism* Caenorhabditis elegans Proteins / chemistry Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* Cell Movement Cell Polarity* Endocytosis* Frizzled Receptors / metabolism* Larva / cytology Multiprotein Complexes / metabolism Neurons / cytology Neurons / metabolism Phosphoproteins / chemistry Phosphoproteins / genetics Phosphoproteins / metabolism* Wnt Signaling Pathway*
IF 5.763
Times Cited 1
C.elegans tm1422