Abstract
The overexpression of certain membrane proteins is accompanied by a striking proliferation of intracellular membranes. One of the best characterized inducers of membrane proliferation is the 180-kD mammalian ribosome receptor (p180), whose expression in yeast results in increases in levels of mRNAs encoding proteins that function in the secretory pathway, and an elevation in the cell's ability to secrete proteins. In this study we demonstrate that neither the unfolded protein response nor increased transcription accounts for membrane proliferation or the observed increase in secretory pathway mRNAs. Rather, p180-induced up-regulation of certain secretory pathway transcripts is due to a p180-mediated increase in the longevity of these mRNA species, as determined by measurements of transcriptional activity and specific mRNA turnover. Moreover, we show that the longevity of mRNA in general is substantially promoted through the process of its targeting to the membrane of the endoplasmic reticulum. With respect to the terminal differentiation of secretory tissues, results from this model system provide insights into how the expression of a single protein, p180, could result in substantial morphological and functional changes.
MeSH Terms
Bodily Secretions/physiology
Cells, Cultured
Endoplasmic Reticulum/metabolism,ultrastructure
ErbB Receptors/metabolism
Fungal Proteins/genetics,metabolism
Gene Expression Regulation, Fungal/physiology
HSP70 Heat-Shock Proteins/genetics,metabolism
Intracellular Membranes/metabolism,ultrastructure
Lipids/biosynthesis
Membrane Glycoproteins/genetics,metabolism
Microscopy, Electron
Protein Folding
Protein Serine-Threonine Kinases
RNA, Messenger/metabolism
Receptor, ErbB-4
Receptors, Cytoplasmic and Nuclear/metabolism
Saccharomyces cerevisiae/metabolism,ultrastructure
Saccharomyces cerevisiae Proteins
Transcription, Genetic/physiology
Chemicals
Fungal Proteins
HSP70 Heat-Shock Proteins
KAR2 protein, yeast
Lipids
Membrane Glycoproteins
RNA, Messenger
Receptors, Cytoplasmic and Nuclear
Saccharomyces cerevisiae Proteins
ribosome receptor
IRE1 protein, S cerevisiae
ErbB Receptors
Receptor, ErbB-4
Protein Serine-Threonine Kinases
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Hyde Maureen
Department of Biological Chemistry, University of California, Los Angeles, School of Medicine, Los Angeles, CA 90024, USA.
Block-Alper Laura
Felix Jahaira
Webster Paul
Meyer David I
References (32)
32 references, click to expand
-
Functional and genomic analyses reveal an essential coordination between the unfolded protein response and ER-associated degradation.
Cell. 2000 Apr 28;101(3):249-58
PMID: 10847680
-
Expression of the 180-kD ribosome receptor induces membrane proliferation and increased secretory activity in yeast.
J Cell Biol. 1999 Jul 26;146(2):273-84
PMID: 10427084
-
Intracellular signaling from the endoplasmic reticulum to the nucleus: the unfolded protein response in yeast and mammals.
Curr Opin Cell Biol. 2001 Jun;13(3):349-55
PMID: 11343907
-
The unfolded protein response: no longer just a special teams player.
Traffic. 2001 Aug;2(8):515-23
PMID: 11489209
-
IN02, a positive regulator of lipid biosynthesis, is essential for the formation of inducible membranes in yeast.
Mol Biol Cell. 2002 Jan;13(1):40-51
PMID: 11809821
-
Direct association of messenger RNA with microsomal membranes in human diploid fibroblasts.
J Cell Biol. 1975 Jun;65(3):513-28
PMID: 1133114
-
Cell cycle control of the yeast HO gene: cis- and trans-acting regulators.
Cell. 1987 Feb 13;48(3):389-97
PMID: 3542227
-
Increased amounts of HMG-CoA reductase induce "karmellae": a proliferation of stacked membrane pairs surrounding the yeast nucleus.
J Cell Biol. 1988 Jul;107(1):101-14
PMID: 3292536
-
A system of shuttle vectors and yeast host strains designed for efficient manipulation of DNA in Saccharomyces cerevisiae.
Genetics. 1989 May;122(1):19-27
PMID: 2659436
-
Role of messenger RNA subcellular localization in the posttranscriptional regulation of human histone gene expression.
J Cell Physiol. 1990 Jul;144(1):175-82
PMID: 2365742
-
Measurement of mRNA decay rates in Saccharomyces cerevisiae.
Methods Enzymol. 1991;194:415-23
PMID: 2005800
-
IRE1 encodes a putative protein kinase containing a membrane-spanning domain and is required for inositol phototrophy in Saccharomyces cerevisiae.
Mol Microbiol. 1992 Jun;6(11):1441-6
PMID: 1625574
-
A 22 bp cis-acting element is necessary and sufficient for the induction of the yeast KAR2 (BiP) gene by unfolded proteins.
EMBO J. 1992 Jul;11(7):2583-93
PMID: 1628622
-
The promoter region of the yeast KAR2 (BiP) gene contains a regulatory domain that responds to the presence of unfolded proteins in the endoplasmic reticulum.
Mol Cell Biol. 1993 Feb;13(2):877-90
PMID: 8423809
-
Vps1p, a member of the dynamin GTPase family, is necessary for Golgi membrane protein retention in Saccharomyces cerevisiae.
EMBO J. 1993 Aug;12(8):3049-59
PMID: 8344247
-
Construction of a set of convenient Saccharomyces cerevisiae strains that are isogenic to S288C.
Yeast. 1995 Jan;11(1):53-5
PMID: 7762301
-
Studies on the transformation of intact yeast cells by the LiAc/SS-DNA/PEG procedure.
Yeast. 1995 Apr 15;11(4):355-60
PMID: 7785336
-
Functional characterization of the 180-kD ribosome receptor in vivo.
J Cell Biol. 1995 Jul;130(1):29-39
PMID: 7790375
-
Reliable method to prepare RNA from free and membrane-bound polysomes from different yeast species.
Biotechniques. 1995 Apr;18(4):564-6, 568
PMID: 7598881
-
Identification of the sequences in HMG-CoA reductase required for karmellae assembly.
Mol Biol Cell. 1995 Nov;6(11):1535-47
PMID: 8589454
-
Topogenesis of a microsomal cytochrome P450 and induction of endoplasmic reticulum membrane proliferation in Saccharomyces cerevisiae.
Arch Biochem Biophys. 1996 Jun 1;330(1):97-109
PMID: 8651709
-
Different subcellular localization of Saccharomyces cerevisiae HMG-CoA reductase isozymes at elevated levels corresponds to distinct endoplasmic reticulum membrane proliferations.
Mol Biol Cell. 1996 May;7(5):769-89
PMID: 8744950
-
Signalling from endoplasmic reticulum to nucleus: transcription factor with a basic-leucine zipper motif is required for the unfolded protein-response pathway.
Genes Cells. 1996 Sep;1(9):803-17
PMID: 9077435
-
A set of vectors with a tetracycline-regulatable promoter system for modulated gene expression in Saccharomyces cerevisiae.
Yeast. 1997 Jul;13(9):837-48
PMID: 9234672
-
The unfolded protein response coordinates the production of endoplasmic reticulum protein and endoplasmic reticulum membrane.
Mol Biol Cell. 1997 Sep;8(9):1805-14
PMID: 9307975
-
Inducible membranes in yeast: relation to the unfolded-protein-response pathway.
Yeast. 1997 Oct;13(13):1211-29
PMID: 9364746
-
Overexpression of Pex15p, a phosphorylated peroxisomal integral membrane protein required for peroxisome assembly in S.cerevisiae, causes proliferation of the endoplasmic reticulum membrane.
EMBO J. 1997 Dec 15;16(24):7326-41
PMID: 9405362
-
Designer deletion strains derived from Saccharomyces cerevisiae S288C: a useful set of strains and plasmids for PCR-mediated gene disruption and other applications.
Yeast. 1998 Jan 30;14(2):115-32
PMID: 9483801
-
Null mutation in IRE1 gene inhibits overproduction of microsomal cytochrome P450Alk1 (CYP 52A3) and proliferation of the endoplasmic reticulum in Saccharomyces cerevisiae.
J Biochem. 1999 Mar;125(3):507-14
PMID: 10050038
-
The cis acting sequences responsible for the differential decay of the unstable MFA2 and stable PGK1 transcripts in yeast include the context of the translational start codon.
RNA. 1999 Mar;5(3):420-33
PMID: 10094310
-
Enlargement of the endoplasmic reticulum membrane in Saccharomyces cerevisiae is not necessarily linked to the unfolded protein response via Ire1p.
FEBS Lett. 1999 Jun 18;453(1-2):210-4
PMID: 10403405
-
A regulatory link between ER-associated protein degradation and the unfolded-protein response.
Nat Cell Biol. 2000 Jul;2(7):379-84
PMID: 10878801