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PMID: 8744950 Published · ppublish English Journal Article Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S.

Different subcellular localization of Saccharomyces cerevisiae HMG-CoA reductase isozymes at elevated levels corresponds to distinct endoplasmic reticulum membrane proliferations.

Molecular biology of the cell ·Vol. 7 ·No. 5 ·1996-05-00 ·Pages 769-89

Koning AJ, Roberts CJ, Wright RL

Abstract

In all eucaryotic cell types analyzed, proliferations of the endoplasmic reticulum (ER) can be induced by increasing the levels of certain integral ER proteins. One of the best characterized of these proteins is HMG-CoA reductase, which catalyzes the rate-limiting step in sterol biosynthesis. We have investigated the subcellular distributions of the two HMG-CoA reductase isozymes in Saccharomyces cerevisiae and the types of ER proliferations that arise in response to elevated levels of each isozyme. At endogenous expression levels, Hmg1p and Hmg2p were both primarily localized in the nuclear envelope. However, at increased levels, the isozymes displayed distinct subcellular localization patterns in which each isozyme was predominantly localized in a different region of the ER. Specifically, increased levels of Hmg1p were concentrated in the nuclear envelope, whereas increased levels of Hmg2p were concentrated in the peripheral ER. In addition, an Hmg2p chimeric protein containing a 77-amino acid lumenal segment from Hmg1p was localized in a pattern that resembled that of Hmg1p when expressed at increased levels. Reflecting their different subcellular distributions, elevated levels of Hmg1p and Hmg2p induced sets of ER membrane proliferations with distinct morphologies. The ER membrane protein, Sec61p, was localized in the membranes induced by both Hmg1p and Hmg2p green fluorescent protein (GFP) fusions. In contrast, the lumenal ER protein, Kar2p, was present in Hmg1p:GFP membranes, but only rarely in Hmg2p:GFP membranes. These results indicated that the membranes synthesized in response to Hmg1p and Hmg2p were derived from the ER, but that the membranes were not identical in protein composition. We determined that the different types of ER proliferations were not simply due to quantitative differences in protein amounts or to the different half-lives of the two isozymes. It is possible that the specific distributions of the two yeast HMG-CoA reductase isozymes and their corresponding membrane proliferations may reveal regions of the ER that are specialized for certain branches of the sterol biosynthetic pathway.

MeSH Terms
Endoplasmic Reticulum/enzymology,physiology,ultrastructure Hydroxymethylglutaryl CoA Reductases/metabolism,ultrastructure Immunohistochemistry Intracellular Membranes/drug effects,enzymology,ultrastructure Isoenzymes/metabolism,ultrastructure Lovastatin/pharmacology Microscopy, Confocal Microscopy, Electron Plasmids Saccharomyces cerevisiae/enzymology,ultrastructure
Chemicals
Isoenzymes Lovastatin Hydroxymethylglutaryl CoA Reductases
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Koning A J
Department of Zoology, University of Washington, Seattle 98195, USA.
Roberts C J
Wright R L
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Article Info
Journal
Molecular biology of the cell
Abbr.
Mol Biol Cell
ISSN
1059-1524
DOI
10.1091/mbc.7.5.769
Published
1996-05-00
Pages
769-89
Language
English
Region
United States
NLM ID
9201390
PMCID
PMC275929
Subset
IM
Grants
NIGMS NIH HHS · 5T32GM-07270-27 · United States
NIGMS NIH HHS · GM-45726 · United States
External Links
PubMed source DOI: 10.1091/mbc.7.5.769 PMC Full Text View journal details
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