Vangl2 regulates E-cadherin in epithelial cells

Sci Rep. 2014 Nov 6;4:6940. doi: 10.1038/srep06940.

Abstract

E-cadherin belongs to the classic cadherin subfamily of calcium-dependent cell adhesion molecules and is crucial for the formation and function of epithelial adherens junctions. In this study, we demonstrate that Vangl2, a vertebrate regulator of planar cell polarity (PCP), controls E-cadherin in epithelial cells. E-cadherin co-immunoprecipitates with Vangl2 from embryonic kidney extracts, and this association is also observed in transfected fibroblasts. Vangl2 enhances the internalization of E-cadherin when overexpressed. Conversely, the quantitative ratio of E-cadherin exposed to the cell surface is increased in cultured renal epithelial cells derived from Vangl2(Lpt/+) mutant mice. Interestingly, Vangl2 is also internalized through protein traffic involving Rab5- and Dynamin-dependent endocytosis. Taken together with recent reports regarding the transport of Frizzled3, MMP14 and nephrin, these results suggest that one of the molecular functions of Vangl2 is to enhance the internalization of specific plasma membrane proteins with broad selectivity. This function may be involved in the control of intercellular PCP signalling or in the PCP-related rearrangement of cell adhesions.

MeSH terms

  • Adherens Junctions / metabolism*
  • Adherens Junctions / ultrastructure
  • Animals
  • Cadherins / genetics*
  • Cadherins / metabolism
  • Cell Adhesion
  • Cell Count
  • Cell Membrane / metabolism*
  • Cell Polarity
  • Dynamins / genetics
  • Dynamins / metabolism
  • Embryo, Mammalian
  • Endocytosis
  • Epithelial Cells / metabolism*
  • Epithelial Cells / ultrastructure
  • Fibroblasts / metabolism
  • Fibroblasts / ultrastructure
  • Gene Expression Regulation
  • Kidney / cytology
  • Kidney / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Nerve Tissue Proteins / genetics*
  • Nerve Tissue Proteins / metabolism
  • Protein Transport
  • Signal Transduction
  • rab5 GTP-Binding Proteins / genetics
  • rab5 GTP-Binding Proteins / metabolism

Substances

  • Cadherins
  • Ltap protein, mouse
  • Nerve Tissue Proteins
  • rab5 GTP-Binding Proteins
  • Dynamins