Loss of eEF1A2 (Eukaryotic Elongation Factor 1 A2) in Murine Myocardium Results in Dilated Cardiomyopathy

ABSTRACT 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.

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Sequence of a fission yeast gene encoding a protein with extensive homology to eukaryotic elongation factor-1 γ

Gene ◽

10.1016/0378-1119(93)90184-5 ◽

1993 ◽

Vol 134 (1) ◽

pp. 119-122 ◽

Cited By ~ 4

Author(s):

Momoi Hiroyuki ◽

Yamada Hisami ◽

Ueguchi Chiharu ◽

Mizuno Takeshi

Keyword(s):

Fission Yeast ◽

Elongation Factor ◽

Yeast Gene ◽

Gene Encoding ◽

Eukaryotic Elongation Factor ◽

Elongation Factor 1

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Immunofluorescence studies of human fibroblasts demonstrate the presence of the complex of elongation factor-1 beta gamma delta in the endoplasmic reticulum

Journal of Cell Science ◽

10.1242/jcs.109.5.1113 ◽

1996 ◽

Vol 109 (5) ◽

pp. 1113-1117 ◽

Cited By ~ 2

Author(s):

J. Sanders ◽

M. Brandsma ◽

G.M. Janssen ◽

J. Dijk ◽

W. Moller

Keyword(s):

Endoplasmic Reticulum ◽

Human Fibroblasts ◽

Intracellular Localization ◽

Elongation Factor ◽

Guanine Nucleotide ◽

Nucleotide Exchange ◽

Gamma Delta ◽

Eukaryotic Elongation Factor ◽

Guanine Nucleotide Binding ◽

Elongation Factor 1

The eukaryotic elongation factor-1 (EF-1) consists of four subunits, EF-1 alpha, EF-1 beta, EF-1 gamma and EF-1 delta which induce efficient transfer of aminoacyl-tRNA to the ribosome. In this process EF-1 alpha.GTP acts as the carrier of the aminoacyl-tRNA on its way to the ribosome. After release of aminoacyl-tRNA to the ribosome under concomitant hydrolysis of GTP, the inactive EF-1 alpha.GDP form is recycled to EF-1 alpha.GTP by EF-1 beta gamma delta. In eukaryotic cells the concentration of EF-1 alpha exceeds that of the complex beta gamma delta by a factor of 5–10. In order to delineate the intracellular localization of the different subunits of EF-1, antibodies against the EF-1 subunits have been elicited and indirect immunofluorescence microscopy experiments were performed. In human fibroblasts, the guanine nucleotide exchange part of EF-1, EF-1 beta gamma delta, was found to co-localize with the endoplasmic reticulum (ER), displaying a distinct fine-structure in its staining pattern. The guanine nucleotide-binding subunit of EF-1, EF-1 alpha, shows a more diffuse distribution throughout the cytoplasm and is, in addition, associated with the nucleus.

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