SASH1 regulates melanocyte transepithelial migration through a novel Gαs-SASH1-IQGAP1-E-Cadherin dependent pathway

Cell Signal. 2013 Jun;25(6):1526-38. doi: 10.1016/j.cellsig.2012.12.025. Epub 2013 Jan 16.


One important function of melanocytes (MCs) is to produce and transfer melanin to neighbouring keratinocytes (KCs) to protect epithelial cells from UV radiation. The mechanisms regulating the specific migration and localisation of the MC lineage remain unknown. We have found three heterozygous mutations that cause amino acid substitutions in the SASH1 gene in individuals with a kind of dyschromatosis. In epidermal tissues from an affected individual, we observed the increased transepithelial migration of melanocytes. Functional analyses indicate that these SASH1 mutations not only cause the increased migration of A375 cells and but also induce intensive bindings with two novel cell adhesion partners IQGAP1 and Gαs. Further, SASH1 mutations induce uniform loss of E-Cadherin in human A375 cells. Our findings suggest a new scaffold protein SASH1 to regulate IQGAP1-E-Cadherin signalling and demonstrate a novel crosstalking between GPCR signalling, calmodulin signalling for the modulation of MCs invasion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cadherins / metabolism
  • Cell Line
  • Cell Movement
  • GTP-Binding Protein alpha Subunits, Gs / antagonists & inhibitors
  • GTP-Binding Protein alpha Subunits, Gs / genetics
  • GTP-Binding Protein alpha Subunits, Gs / metabolism*
  • HEK293 Cells
  • Humans
  • Melanocytes / cytology*
  • Melanocytes / metabolism
  • Mutation
  • Protein Binding
  • RNA Interference
  • RNA, Small Interfering / metabolism
  • Signal Transduction
  • Transendothelial and Transepithelial Migration
  • Tumor Suppressor Proteins / genetics
  • Tumor Suppressor Proteins / metabolism*
  • ras GTPase-Activating Proteins / antagonists & inhibitors
  • ras GTPase-Activating Proteins / genetics
  • ras GTPase-Activating Proteins / metabolism*


  • Cadherins
  • IQ motif containing GTPase activating protein 1
  • RNA, Small Interfering
  • SASH1 protein, human
  • Tumor Suppressor Proteins
  • ras GTPase-Activating Proteins
  • GTP-Binding Protein alpha Subunits, Gs