RRC ID 29215
Author Sato M, Sato K, Nishikawa S, Hirata A, Kato J, Nakano A.
Title The yeast RER2 gene, identified by endoplasmic reticulum protein localization mutations, encodes cis-prenyltransferase, a key enzyme in dolichol synthesis.
Journal Mol Cell Biol
Abstract As an approach to understand the molecular mechanisms of endoplasmic reticulum (ER) protein sorting, we have isolated yeast rer mutants that mislocalize a Sec12-Mfalpha1p fusion protein from the ER to later compartments of the secretory pathway (S. Nishikawa and A. Nakano, Proc. Natl. Acad. Sci. USA 90:8179-8183, 1993). The temperature-sensitive rer2 mutant mislocalizes different types of ER membrane proteins, suggesting that RER2 is involved in correct localization of ER proteins in general. The rer2 mutant shows several other characteristic phenotypes: slow growth, defects in N and O glycosylation, sensitivity to hygromycin B, and abnormal accumulation of membranes, including the ER and the Golgi membranes. RER2 and SRT1, a gene whose overexpression suppresses rer2, encode novel proteins similar to each other, and their double disruption is lethal. RER2 homologues are found not only in eukaryotes but also in many prokaryote species and thus constitute a large gene family which has been well conserved during evolution. Taking a hint from the phenotype of newly established mutants of the Rer2p homologue of Escherichia coli, we discovered that the rer2 mutant is deficient in the activity of cis-prenyltransferase, a key enzyme of dolichol synthesis. This and other lines of evidence let us conclude that members of the RER2 family of genes encode cis-prenyltransferase itself. The difference in phenotypes between the rer2 mutant and previously obtained glycosylation mutants suggests a novel, as-yet-unknown role of dolichol.
Volume 19(1)
Pages 471-83
Published 1999-1-1
DOI 10.1128/mcb.19.1.471
PMID 9858571
PMC PMC83905
MeSH Alkyl and Aryl Transferases / genetics* Alkyl and Aryl Transferases / physiology Amino Acid Sequence Animals Cloning, Molecular Dolichols / biosynthesis* Endoplasmic Reticulum / metabolism Fungal Proteins / genetics Fungal Proteins / metabolism Genes, Fungal Glycosylation Guanine Nucleotide Exchange Factors Heat-Shock Proteins* Intracellular Membranes Membrane Glycoproteins / genetics Membrane Glycoproteins / metabolism Membrane Proteins / genetics Membrane Proteins / metabolism Membrane Transport Proteins* Molecular Sequence Data Mutagenesis Rabbits Recombinant Fusion Proteins / genetics Recombinant Fusion Proteins / metabolism Saccharomyces cerevisiae / enzymology* Saccharomyces cerevisiae / genetics Saccharomyces cerevisiae Proteins / genetics* Saccharomyces cerevisiae Proteins / physiology Subcellular Fractions Transferases / genetics* Transferases / physiology
IF 3.611
Times Cited 122
WOS Category BIOCHEMISTRY & MOLECULAR BIOLOGY CELL BIOLOGY
Resource
DNA material rer2::LEU2 (RDB08836) pRER206 SRT1disruption (RDB08837) pY1 (RDB08835) pR7 (RDB08838) pR7HA (RDB08839) pR7HA-4 (RDB08840) pR7HA-2 (RDB08841)