This Article Full Text Full Text (PDF) Other Versions of this Article: MCB.00150-08v1 28/14/4549    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Google Scholar Articles by Jeganathan, S. Articles by Lee, J. M. PubMed PubMed Citation Articles by Jeganathan, S. Articles by Lee, J. M.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, July 2008, p. 4549-4561, Vol. 28, No. 14
0270-7306/08/$08.00+0     doi:10.1128/MCB.00150-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Eukaryotic Elongation Factor 1A2 Cooperates with Phosphatidylinositol-4 Kinase III β To Stimulate Production of Filopodia through Increased Phosphatidylinositol-4,5 Bisphosphate Generation

Department of Biochemistry, Microbiology, and Immunology, University of Ottawa, 451 Smyth Road, Ottawa, Ontario, Canada K1H 8M5

Received 21 January 2008/ Returned for modification 4 March 2008/ Accepted 5 May 2008

Eukaryotic elongation factor 1 alpha 2 (eEF1A2) is a transforming gene product that is highly expressed in human tumors of the ovary, lung, and breast. eEF1A2 also stimulates actin remodeling, and the expression of this factor is sufficient to induce the formation of filopodia, long cellular processes composed of bundles of parallel actin filaments. Here, we find that eEF1A2 stimulates formation of filopodia by increasing the cellular abundance of cytosolic and plasma membrane-bound phosphatidylinositol-4,5 bisphosphate [PI(4,5)P₂]. We have previously reported that the eEF1A2 protein binds and activates phosphatidylinositol-4 kinase III beta (PI4KIIIβ), and we find that production of eEF1A2-dependent PI(4,5)P₂ and generation of filopodia require PI4KIIIβ. Furthermore, PI4KIIIβ is itself capable of activating both the production of PI(4,5)P₂ and the creation of filopodia. We propose a model for extrusion of filopodia in which eEF1A2 activates PI4KIIIβ, and activated PI4KIIIβ stimulates production of PI(4,5)P₂ and filopodia by increasing PI4P abundance. Our work suggests an important role for both eEF1A2 and PI4KIIIβ in the control of PI(4,5)P₂ signaling and actin remodeling.

Published ahead of print on 12 May 2008.