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Molecular and Cellular Biology, March 2007, p. 1974-1989, Vol. 27, No. 5
0270-7306/07/$08.00+0     doi:10.1128/MCB.00832-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Improper Organization of the Actin Cytoskeleton Affects Protein Synthesis at Initiation{triangledown}

Stephane R. Gross and Terri Goss Kinzy*

Department of Molecular Genetics, Microbiology and Immunology, Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, Piscataway, New Jersey 08854

Received 10 May 2006/ Returned for modification 14 June 2006/ Accepted 7 December 2006

Although the actin cytoskeleton and the translation machinery are considered to be separate cellular complexes, growing evidence supports overlapping regulation of the two systems. Because of its interaction with actin, the eukaryotic translation elongation factor 1A (eEF1A) is proposed to be a regulator or link between these processes. Using a genetic approach with the yeast Saccharomyces cerevisiae, specific regions of eEF1A responsible for actin interactions and bundling were identified. Five new mutations were identified along one face of eEF1A. Dramatic changes in cell growth, cell morphology, and actin cable and patch formation as well as a unique effect on total translation in strains expressing the F308L or S405P eEF1A mutant form were observed. The translation effects do not correlate with reduced translation elongation but instead include an initiation defect. Biochemical analysis of the eEF1A mutant forms demonstrated reduced actin-bundling activity in vitro. Reduced total translation and/or the accumulation of 80S ribosomes in strains with either a mutation or a null allele of genes encoding actin itself or actin-regulating proteins Tpm1p, Mdm20p, and Bnirp/Bni1p was observed. Our data demonstrate that eEF1A, other actin binding proteins, and actin mutants affect translation initiation through the actin cytoskeleton.


* Corresponding author. Mailing address: Department of Molecular Genetics, Microbiology and Immunology, Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, Piscataway, NJ 08854. Phone: (732) 235-5450. Fax: (732) 235-5223. E-mail: kinzytg{at}umdnj.edu.

{triangledown} Published ahead of print on 18 December 2006.


Molecular and Cellular Biology, March 2007, p. 1974-1989, Vol. 27, No. 5
0270-7306/07/$08.00+0     doi:10.1128/MCB.00832-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.




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