Eukaryotic elongation factor 1A2 cooperates with phosphatidylinositol-4 kinase III beta to stimulate production of filopodia through increased phosphatidylinositol-4,5 bisphosphate generation.
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)P(2)]. We have previously reported that the eEF1A2 protein binds and activates phosphatidylinositol-4 kinase III beta (PI4KIIIbeta), and we find that production of eEF1A2-dependent PI(4,5)P(2) and generation of filopodia require PI4KIIIbeta. Furthermore, PI4KIIIbeta is itself capable of activating both the production of PI(4,5)P(2) and the creation of filopodia. We propose a model for extrusion of filopodia in which eEF1A2 activates PI4KIIIbeta, and activated PI4KIIIbeta stimulates production of PI(4,5)P(2) and filopodia by increasing PI4P abundance. Our work suggests an important role for both eEF1A2 and PI4KIIIbeta in the control of PI(4,5)P(2) signaling and actin remodeling.
Jeganathan
Sujeeve
S
Department of Biochemistry, University of Ottawa, 451 Smyth Road, Ottawa, Ontario, Canada.
Morrow
Anne
A
Amiri
Anahita
A
Lee
Jonathan M
JM
D019870:1-Phosphatidylinositol 4-Kinase / Q000378:metabolism*; D000818:Animals; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D020648:Peptide Elongation Factor 1 / Q000378:metabolism*; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000032:analysis / Q000378:metabolism*; D011554:Pseudopodia / Q000378:metabolism*; D051381:Rats; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism
C503234:EEF1A2 protein, human; C503236:Eef1a2 protein, rat; D020648:Peptide Elongation Factor 1; D019269:Phosphatidylinositol 4,5-Diphosphate; D019870:1-Phosphatidylinositol 4-Kinase; D020764:cdc42 GTP-Binding Protein