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PMID: 8524255 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Mutations altering the mitochondrial-cytoplasmic distribution of Mod5p implicate the actin cytoskeleton and mRNA 3' ends and/or protein synthesis in mitochondrial delivery.

Molecular and cellular biology ·Vol. 15 ·No. 12 ·1995-12-00 ·Pages 6884-94

Zoladek T, Vaduva G, Hunter LA, Boguta M, Go BD, Martin NC, Hopper AK

Abstract

The Saccharomyces cerevisiae MOD5 gene encodes proteins that function in three subcellular locations: mitochondria, the cytoplasm, and nuclei (M. Boguta, L.A. Hunter, W.-C. Shen, E. C. Gillman, N. C. Martin, and A. K. Hopper, Mol. Cell. Biol. 14:2298-2306, 1994; E. C. Gillman, L. B. Slusher, N. C. Martin, and A. K. Hopper, Mol. Cell. Biol. 11:2382-2390, 1991). A mutant allele of MOD5 encoding a protein (Mod5p-I,KR6) located predominantly in mitochondria was constructed. Mutants defective in delivering Mod5p-I,KR6 to mitochondria were sought by selecting cells with increased cytosolic activity of this protein. Twenty-five mutants defining four complementation groups, mdp1, mdp2, mdp3, and mdp4, were found. They are unable to respire at 34 degrees C or to grow on glucose medium at 38 degrees C. Cell fractionation studies showed that mdp1, mdp2, and mdp3 mutants have an altered mitochondrial-cytoplasmic distribution of Mod5p. mdp2 can be suppressed by ACT1, the actin-encoding gene. The actin cytoskeleton organization is also aberrant in mdp2 cells. MDP2 is the same as VRP1 (S. F. H. Donnelly, M. J. Picklington, D. Pallotta, and E. Orr, Mol. Microbiol. 10:585-596, 1993). MDP3 is identical to PAN1, which encodes a protein that interacts with mRNA 3' ends and affects initiation of protein synthesis (A. B. Sachs and J. A. Deardoff, Cell 70:961-973, 1992). These results implicate the actin cytoskeleton and mRNA 3' ends and/or protein synthesis as being as important for protein distribution in S. cerevisiae as they are for distribution of cytosolic proteins in higher eukaryotes. This provides the potential to apply genetic and molecular approaches to study gene products and mechanisms involved in this type of protein distribution. The selection strategy also offers a new approach for identifying gene products involved in the distribution of proteins to their subscellular destinations.

MeSH Terms
Actins/metabolism Alkyl and Aryl Transferases Amino Acid Sequence Base Sequence Cytoplasm/metabolism Cytoskeleton/metabolism Enzymes/metabolism Fluorescent Antibody Technique, Indirect Genes, Fungal Genes, Suppressor Genetic Complementation Test Genotype Mitochondria/metabolism Molecular Sequence Data Mutagenesis, Site-Directed Oligodeoxyribonucleotides Protein Biosynthesis Proteins/genetics,metabolism RNA, Messenger/genetics,metabolism Saccharomyces cerevisiae/genetics,metabolism Saccharomyces cerevisiae Proteins
Chemicals
Actins Enzymes Oligodeoxyribonucleotides Proteins RNA, Messenger Saccharomyces cerevisiae Proteins Alkyl and Aryl Transferases MOD5 protein, S cerevisiae
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Zoladek T
Department of Biochemistry and Molecular Biology, Milton S. Hershey Medical Center, Pennsylvania State University, Hershey 17033, USA.
Vaduva G
Hunter L A
Boguta M
Go B D
Martin N C
Hopper A K
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
Published
1995-12-00
Pages
6884-94
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC230943
Subset
IM
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