FRMD4A regulates epithelial polarity by connecting Arf6 activation with the PAR complex

Proc Natl Acad Sci U S A. 2010 Jan 12;107(2):748-53. doi: 10.1073/pnas.0908423107. Epub 2009 Dec 22.

Abstract

The Par-3/Par-6/aPKC/Cdc42 complex regulates the conversion of primordial adherens junctions (AJs) into belt-like AJs and the formation of linear actin cables during epithelial polarization. However, the mechanisms by which this complex functions are not well elucidated. In the present study, we found that activation of Arf6 is spatiotemporally regulated as a downstream signaling pathway of the Par protein complex. When primordial AJs are formed, Par-3 recruits a scaffolding protein, termed the FERM domain containing 4A (FRMD4A). FRMD4A connects Par-3 and the Arf6 guanine-nucleotide exchange factor (GEF), cytohesin-1. We propose that the Par-3/FRMD4A/cytohesin-1 complex ensures accurate activation of Arf6, a central player in actin cytoskeleton dynamics and membrane trafficking, during junctional remodeling and epithelial polarization.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adherens Junctions / genetics*
  • Adherens Junctions / physiology
  • Cell Polarity
  • Epithelial Cells / physiology*