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PMID: 11950929 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Yeast genes controlling responses to topogenic signals in a model transmembrane protein.

Molecular biology of the cell ·Vol. 13 ·No. 4 ·2002-04-00 ·Pages 1158-74

Tipper DJ, Harley CA

Abstract

Yeast protein insertion orientation (PIO) mutants were isolated by selecting for growth on sucrose in cells in which the only source of invertase is a C-terminal fusion to a transmembrane protein. Only the fraction with an exocellular C terminus can be processed to secreted invertase and this fraction is constrained to 2-3% by a strong charge difference signal. Identified pio mutants increased this to 9-12%. PIO1 is SPF1, encoding a P-type ATPase located in the endoplasmic reticulum (ER) or Golgi. spf1-null mutants are modestly sensitive to EGTA. Sensitivity is considerably greater in an spf1 pmr1 double mutant, although PIO is not further disturbed. Pmr1p is the Golgi Ca(2+) ATPase and Spf1p may be the equivalent ER pump. PIO2 is STE24, a metalloprotease anchored in the ER membrane. Like Spf1p, Ste24p is expressed in all yeast cell types and belongs to a highly conserved protein family. The effects of ste24- and spf1-null mutations on invertase secretion are additive, cell generation time is increased 60%, and cells become sensitive to cold and to heat shock. Ste24p and Rce1p cleave the C-AAX bond of farnesylated CAAX box proteins. The closest paralog of SPF1 is YOR291w. Neither rce1-null nor yor291w-null mutations affected PIO or the phenotype of spf1- or ste24-null mutants. Mutations in PIO3 (unidentified) cause a weaker Pio phenotype, enhanced by a null mutation in BMH1, one of two yeast 14-3-3 proteins.

MeSH Terms
Adenosine Triphosphatases/metabolism Cell Membrane/metabolism DNA-Binding Proteins/metabolism Ethyl Methanesulfonate/pharmacology Fungal Proteins/metabolism Gene Library Genes, Reporter Genetic Complementation Test Genetic Vectors Glycoside Hydrolases/metabolism Ligases/metabolism Membrane Proteins/metabolism Metalloendopeptidases/metabolism Models, Biological Mutagenesis Mutagens/pharmacology Mutation Phenotype Plant Proteins/metabolism Precipitin Tests Protein Binding Protein Conformation Protein Structure, Tertiary Proteins/metabolism Recombinant Fusion Proteins/metabolism Saccharomyces cerevisiae/metabolism Saccharomyces cerevisiae Proteins Time Factors Ubiquitin-Conjugating Enzymes beta-Fructofuranosidase beta-Galactosidase/metabolism beta-Lactamases/metabolism
Chemicals
DNA-Binding Proteins Fungal Proteins Membrane Proteins Mutagens Plant Proteins Proteins Recombinant Fusion Proteins SPF1 protein, plant Saccharomyces cerevisiae Proteins Ethyl Methanesulfonate UBE2L3 protein, human Ubiquitin-Conjugating Enzymes Glycoside Hydrolases beta-Galactosidase beta-Fructofuranosidase Metalloendopeptidases STE24 protein, S cerevisiae beta-Lactamases Adenosine Triphosphatases Ligases
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Tipper Donald J
Department of Molecular Genetics and Microbiology, University of Massachusetts Medical School, Worcester, MA 01655, USA. [email protected]
Harley Carol A
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Article Info
Journal
Molecular biology of the cell
Abbr.
Mol Biol Cell
ISSN
1059-1524
DOI
10.1091/mbc.01-10-0488
Email
[email protected]
Published
2002-04-00
Pages
1158-74
Language
English
Region
United States
NLM ID
9201390
PMCID
PMC102259
Subset
IM
External Links
PubMed source DOI: 10.1091/mbc.01-10-0488 PMC Full Text View journal details
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