Integrin-linked Kinase Interactions with ELMO2 Modulate Cell Polarity

Authors

Ernest Ho, University of Western Ontario
Tames Irvine, University of Western Ontario
Gregory J. A. Vilk, University of Western Ontario
Gilles Lajoie, University of Western Ontario
Kodi S. Ravichandran, University of Virginia
Sudhir J. A. D'Souza, University of Western Ontario
Lina Dagnino, University of Western Ontario

Document Type

Article

Publication Date

7-1-2009

Journal

Molecular Biology of the Cell

Volume

20

Issue

13

First Page

3033

Last Page

3043

URL with Digital Object Identifier

10.1091/mbc.E09-01-0050

Abstract

Cell polarization is a key prerequisite for directed migration during development, tissue regeneration, and metastasis. Integrin-linked kinase (ILK) is a scaffold protein essential for cell polarization, but very little is known about the precise mechanisms whereby ILK modulates polarization in normal epithelia. Elucidating these mechanisms is essential to understand tissue morphogenesis, transformation, and repair. Here we identify a novel ILK protein complex that includes Engulfment and Cell Motility 2 (ELMO2). We also demonstrate the presence of RhoG in ILK-ELMO2 complexes, and the localization of this multiprotein species specifically to the leading lamellipodia of polarized cells. Significantly, the ability of RhoG to bind ELMO is crucial for ILK induction of cell polarization, and the joint expression of ILK and ELMO2 synergistically promotes the induction of front-rear polarity and haptotactic migration. This places RhoG-ELMO2-ILK complexes in a key position for the development of cell polarity and forward movement. Although ILK is a component of many diverse multiprotein species that may contribute to cell polarization, expression of dominant-negative ELMO2 mutants is sufficient to abolish the ability of ILK to promote cell polarization. Thus, its interaction with ELMO2 and RhoG is essential for the ability of ILK to induce front-rear cell polarity.