Ezrin interacts with the scaffold protein IQGAP1 and affects its cortical localization

Biochim Biophys Acta. 2015 Sep;1853(9):2086-94. doi: 10.1016/j.bbamcr.2014.12.026. Epub 2014 Dec 30.

Abstract

The cortical cytoskeleton constitutes an important subcellular structure that determines cell shape and regulates cell migration as well as membrane traffic to and from the plasma membrane. Many components of the cortical cytoskeleton have been identified including structural and scaffolding proteins, membrane-cytoskeleton linker proteins and signaling intermediates. We describe here an association of the membrane-F-actin linker protein ezrin with the scaffolding protein IQGAP1 that serves as a hub for concentrating different signaling complexes. Both, ezrin and IQGAP1 bind in a Ca²⁺-dependent manner to the EF hand protein S100P and complexes consisting of Ca²⁺-bound S100P, IQGAP1 and ezrin can be isolated by immunoprecipitation. Ezrin and IQGAP1 also interact in the absence of Ca²⁺, thus independent of S100P. Direct ezrin-IQGAP1 interaction can be shown with the purified proteins. It is mediated via the N-terminal FERM domain of ezrin and the IQ domain of IQGAP1, respectively. Ezrin and IQGAP1 colocalize in the submembraneous cytoskeleton and in cellular protrusions of human epithelial cells and knockdown of ezrin reduces the cortical localization of IQGAP1. Thus, ezrin appears to participate in recruiting IQGAP1 to the cell cortex thereby establishing a close connection between membrane-F-actin contacts and actin regulators that can be assembled by IQGAP1. This article is part of a Special Issue entitled: 13th European Symposium on Calcium.

Keywords: Actin; Calcium-binding protein; Cell cortex; EF hand; Membrane.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Calcium / metabolism*
  • Calcium-Binding Proteins / genetics
  • Calcium-Binding Proteins / metabolism*
  • Cytoskeletal Proteins / genetics
  • Cytoskeletal Proteins / metabolism*
  • Cytoskeleton / genetics
  • Cytoskeleton / metabolism*
  • HEK293 Cells
  • HeLa Cells
  • Humans
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism*
  • Protein Binding
  • ras GTPase-Activating Proteins / genetics
  • ras GTPase-Activating Proteins / metabolism*

Substances

  • Calcium-Binding Proteins
  • Cytoskeletal Proteins
  • IQ motif containing GTPase activating protein 1
  • Neoplasm Proteins
  • S100P protein, human
  • ezrin
  • ras GTPase-Activating Proteins
  • Calcium