Identification of the sequences in HMG-CoA reductase required for karmellae assembly

Mark L. Parrish, Christian Sengstag, Jasper D. Rine, Robin L. Wright

Research output: Contribution to journalArticle

46 Citations (Scopus)

Abstract

In all eukaryotic cells that have been examined, specific membrane arrays are induced in response to increased levels of the ER membrane protein, HMG- CoA reductase. Analysis of these inducible membranes has the potential to reveal basic insights into general membrane assembly. Yeast express two HMG- CoA reductase isozymes, and each isozyme induces a morphologically distinct proliferation of the endoplasmic reticulum. The isozyme encoded by HMG1 induces karmellae, which are long stacks of membranes that partially enclose the nucleus. In contrast, the isozyme encoded by HMG2 induces short stacks of membrane that may be associated with the nucleus, but are frequently present at the cell periphery. To understand the molecular nature of the different cellular responses to Hmg1p and Hmg2p, we mapped the region of Hmg1p that is needed for karmellae assembly. For this analysis, a series of exchange alleles was examined in which a portion of the Hmg2p membrane domain was replaced with the corresponding Hmg1p sequences. Results of this analysis indicated that the ER lumenal loop between predicted transmembrane domains 6 and 7 was both necessary and sufficient for karmellae assembly, when present in the context of an HMG-CoA reductase membrane domain. Immunoblotting experiments ruled out the simple possibility that differences in the amounts of the various chimeric HMG-CoA reductase proteins was responsible for the altered cellular responses. Our results are consistent with the hypothesis that each yeast isozyme induces or organizes a qualitatively different organization of ER membrane.

Original languageEnglish (US)
Pages (from-to)1535-1547
Number of pages13
JournalMolecular Biology of the Cell
Volume6
Issue number11
DOIs
StatePublished - Jan 1 1995

Fingerprint

Hydroxymethylglutaryl CoA Reductases
Isoenzymes
Membranes
HMGB2 Protein
Yeasts
HMGB1 Protein
Eukaryotic Cells
Immunoblotting
Endoplasmic Reticulum
Membrane Potentials
Membrane Proteins
Alleles

Cite this

Identification of the sequences in HMG-CoA reductase required for karmellae assembly. / Parrish, Mark L.; Sengstag, Christian; Rine, Jasper D.; Wright, Robin L.

In: Molecular Biology of the Cell, Vol. 6, No. 11, 01.01.1995, p. 1535-1547.

Research output: Contribution to journalArticle

Parrish, Mark L. ; Sengstag, Christian ; Rine, Jasper D. ; Wright, Robin L. / Identification of the sequences in HMG-CoA reductase required for karmellae assembly. In: Molecular Biology of the Cell. 1995 ; Vol. 6, No. 11. pp. 1535-1547.
@article{ca1764f3807c4471b76d573d96cdb375,
title = "Identification of the sequences in HMG-CoA reductase required for karmellae assembly",
abstract = "In all eukaryotic cells that have been examined, specific membrane arrays are induced in response to increased levels of the ER membrane protein, HMG- CoA reductase. Analysis of these inducible membranes has the potential to reveal basic insights into general membrane assembly. Yeast express two HMG- CoA reductase isozymes, and each isozyme induces a morphologically distinct proliferation of the endoplasmic reticulum. The isozyme encoded by HMG1 induces karmellae, which are long stacks of membranes that partially enclose the nucleus. In contrast, the isozyme encoded by HMG2 induces short stacks of membrane that may be associated with the nucleus, but are frequently present at the cell periphery. To understand the molecular nature of the different cellular responses to Hmg1p and Hmg2p, we mapped the region of Hmg1p that is needed for karmellae assembly. For this analysis, a series of exchange alleles was examined in which a portion of the Hmg2p membrane domain was replaced with the corresponding Hmg1p sequences. Results of this analysis indicated that the ER lumenal loop between predicted transmembrane domains 6 and 7 was both necessary and sufficient for karmellae assembly, when present in the context of an HMG-CoA reductase membrane domain. Immunoblotting experiments ruled out the simple possibility that differences in the amounts of the various chimeric HMG-CoA reductase proteins was responsible for the altered cellular responses. Our results are consistent with the hypothesis that each yeast isozyme induces or organizes a qualitatively different organization of ER membrane.",
author = "Parrish, {Mark L.} and Christian Sengstag and Rine, {Jasper D.} and Wright, {Robin L.}",
year = "1995",
month = "1",
day = "1",
doi = "10.1091/mbc.6.11.1535",
language = "English (US)",
volume = "6",
pages = "1535--1547",
journal = "Molecular Biology of the Cell",
issn = "1059-1524",
publisher = "American Society for Cell Biology",
number = "11",

}

TY - JOUR

T1 - Identification of the sequences in HMG-CoA reductase required for karmellae assembly

AU - Parrish, Mark L.

AU - Sengstag, Christian

AU - Rine, Jasper D.

AU - Wright, Robin L.

PY - 1995/1/1

Y1 - 1995/1/1

N2 - In all eukaryotic cells that have been examined, specific membrane arrays are induced in response to increased levels of the ER membrane protein, HMG- CoA reductase. Analysis of these inducible membranes has the potential to reveal basic insights into general membrane assembly. Yeast express two HMG- CoA reductase isozymes, and each isozyme induces a morphologically distinct proliferation of the endoplasmic reticulum. The isozyme encoded by HMG1 induces karmellae, which are long stacks of membranes that partially enclose the nucleus. In contrast, the isozyme encoded by HMG2 induces short stacks of membrane that may be associated with the nucleus, but are frequently present at the cell periphery. To understand the molecular nature of the different cellular responses to Hmg1p and Hmg2p, we mapped the region of Hmg1p that is needed for karmellae assembly. For this analysis, a series of exchange alleles was examined in which a portion of the Hmg2p membrane domain was replaced with the corresponding Hmg1p sequences. Results of this analysis indicated that the ER lumenal loop between predicted transmembrane domains 6 and 7 was both necessary and sufficient for karmellae assembly, when present in the context of an HMG-CoA reductase membrane domain. Immunoblotting experiments ruled out the simple possibility that differences in the amounts of the various chimeric HMG-CoA reductase proteins was responsible for the altered cellular responses. Our results are consistent with the hypothesis that each yeast isozyme induces or organizes a qualitatively different organization of ER membrane.

AB - In all eukaryotic cells that have been examined, specific membrane arrays are induced in response to increased levels of the ER membrane protein, HMG- CoA reductase. Analysis of these inducible membranes has the potential to reveal basic insights into general membrane assembly. Yeast express two HMG- CoA reductase isozymes, and each isozyme induces a morphologically distinct proliferation of the endoplasmic reticulum. The isozyme encoded by HMG1 induces karmellae, which are long stacks of membranes that partially enclose the nucleus. In contrast, the isozyme encoded by HMG2 induces short stacks of membrane that may be associated with the nucleus, but are frequently present at the cell periphery. To understand the molecular nature of the different cellular responses to Hmg1p and Hmg2p, we mapped the region of Hmg1p that is needed for karmellae assembly. For this analysis, a series of exchange alleles was examined in which a portion of the Hmg2p membrane domain was replaced with the corresponding Hmg1p sequences. Results of this analysis indicated that the ER lumenal loop between predicted transmembrane domains 6 and 7 was both necessary and sufficient for karmellae assembly, when present in the context of an HMG-CoA reductase membrane domain. Immunoblotting experiments ruled out the simple possibility that differences in the amounts of the various chimeric HMG-CoA reductase proteins was responsible for the altered cellular responses. Our results are consistent with the hypothesis that each yeast isozyme induces or organizes a qualitatively different organization of ER membrane.

UR - http://www.scopus.com/inward/record.url?scp=0028864187&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0028864187&partnerID=8YFLogxK

U2 - 10.1091/mbc.6.11.1535

DO - 10.1091/mbc.6.11.1535

M3 - Article

VL - 6

SP - 1535

EP - 1547

JO - Molecular Biology of the Cell

JF - Molecular Biology of the Cell

SN - 1059-1524

IS - 11

ER -