Skip to main content
Molecular Biology of the Cell logoLink to Molecular Biology of the Cell
. 1997 Sep;8(9):1805–1814. doi: 10.1091/mbc.8.9.1805

The unfolded protein response coordinates the production of endoplasmic reticulum protein and endoplasmic reticulum membrane.

J S Cox 1, R E Chapman 1, P Walter 1
PMCID: PMC305738  PMID: 9307975

Abstract

The endoplasmic reticulum (ER) is a multifunctional organelle responsible for production of both lumenal and membrane components of secretory pathway compartments. Secretory proteins are folded, processed, and sorted in the ER lumen and lipid synthesis occurs on the ER membrane itself. In the yeast Saccharomyces cerevisiae, synthesis of ER components is highly regulated: the ER-resident proteins by the unfolded protein response and membrane lipid synthesis by the inositol response. We demonstrate that these two responses are intimately linked, forming different branches of the same pathway. Furthermore, we present evidence indicating that this coordinate regulation plays a role in ER biogenesis.

Full text

PDF
1805

Images in this article

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bailis A. M., Poole M. A., Carman G. M., Henry S. A. The membrane-associated enzyme phosphatidylserine synthase is regulated at the level of mRNA abundance. Mol Cell Biol. 1987 Jan;7(1):167–176. doi: 10.1128/mcb.7.1.167. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Basson M. E., Thorsness M., Finer-Moore J., Stroud R. M., Rine J. Structural and functional conservation between yeast and human 3-hydroxy-3-methylglutaryl coenzyme A reductases, the rate-limiting enzyme of sterol biosynthesis. Mol Cell Biol. 1988 Sep;8(9):3797–3808. doi: 10.1128/mcb.8.9.3797. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Carman G. M., Henry S. A. Phospholipid biosynthesis in yeast. Annu Rev Biochem. 1989;58:635–669. doi: 10.1146/annurev.bi.58.070189.003223. [DOI] [PubMed] [Google Scholar]
  4. Cox J. S., Shamu C. E., Walter P. Transcriptional induction of genes encoding endoplasmic reticulum resident proteins requires a transmembrane protein kinase. Cell. 1993 Jun 18;73(6):1197–1206. doi: 10.1016/0092-8674(93)90648-a. [DOI] [PubMed] [Google Scholar]
  5. Cox J. S., Walter P. A novel mechanism for regulating activity of a transcription factor that controls the unfolded protein response. Cell. 1996 Nov 1;87(3):391–404. doi: 10.1016/s0092-8674(00)81360-4. [DOI] [PubMed] [Google Scholar]
  6. Culbertson M. R., Henry S. A. Inositol-requiring mutants of Saccharomyces cerevisiae. Genetics. 1975 May;80(1):23–40. doi: 10.1093/genetics/80.1.23. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Elble R. A simple and efficient procedure for transformation of yeasts. Biotechniques. 1992 Jul;13(1):18–20. [PubMed] [Google Scholar]
  8. Favaloro J., Treisman R., Kamen R. Transcription maps of polyoma virus-specific RNA: analysis by two-dimensional nuclease S1 gel mapping. Methods Enzymol. 1980;65(1):718–749. doi: 10.1016/s0076-6879(80)65070-8. [DOI] [PubMed] [Google Scholar]
  9. Gething M. J., Sambrook J. Protein folding in the cell. Nature. 1992 Jan 2;355(6355):33–45. doi: 10.1038/355033a0. [DOI] [PubMed] [Google Scholar]
  10. Greenberg M. L., Lopes J. M. Genetic regulation of phospholipid biosynthesis in Saccharomyces cerevisiae. Microbiol Rev. 1996 Mar;60(1):1–20. doi: 10.1128/mr.60.1.1-20.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Hirsch J. P., Henry S. A. Expression of the Saccharomyces cerevisiae inositol-1-phosphate synthase (INO1) gene is regulated by factors that affect phospholipid synthesis. Mol Cell Biol. 1986 Oct;6(10):3320–3328. doi: 10.1128/mcb.6.10.3320. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Hood D. A., Balaban A., Connor M. K., Craig E. E., Nishio M. L., Rezvani M., Takahashi M. Mitochondrial biogenesis in striated muscle. Can J Appl Physiol. 1994 Mar;19(1):12–48. doi: 10.1139/h94-002. [DOI] [PubMed] [Google Scholar]
  13. Ito H., Fukuda Y., Murata K., Kimura A. Transformation of intact yeast cells treated with alkali cations. J Bacteriol. 1983 Jan;153(1):163–168. doi: 10.1128/jb.153.1.163-168.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Kodaki T., Hosaka K., Nikawa J., Yamashita S. Identification of the upstream activation sequences responsible for the expression and regulation of the PEM1 and PEM2 genes encoding the enzymes of the phosphatidylethanolamine methylation pathway in Saccharomyces cerevisiae. J Biochem. 1991 Feb;109(2):276–287. [PubMed] [Google Scholar]
  15. Kozutsumi Y., Segal M., Normington K., Gething M. J., Sambrook J. The presence of malfolded proteins in the endoplasmic reticulum signals the induction of glucose-regulated proteins. Nature. 1988 Mar 31;332(6163):462–464. doi: 10.1038/332462a0. [DOI] [PubMed] [Google Scholar]
  16. Mori K., Kawahara T., Yoshida H., Yanagi H., Yura T. 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):803–817. doi: 10.1046/j.1365-2443.1996.d01-274.x. [DOI] [PubMed] [Google Scholar]
  17. Mori K., Ma W., Gething M. J., Sambrook J. A transmembrane protein with a cdc2+/CDC28-related kinase activity is required for signaling from the ER to the nucleus. Cell. 1993 Aug 27;74(4):743–756. doi: 10.1016/0092-8674(93)90521-q. [DOI] [PubMed] [Google Scholar]
  18. Nikawa J., Akiyoshi M., Hirata S., Fukuda T. Saccharomyces cerevisiae IRE2/HAC1 is involved in IRE1-mediated KAR2 expression. Nucleic Acids Res. 1996 Nov 1;24(21):4222–4226. doi: 10.1093/nar/24.21.4222. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Nikawa J., Yamashita S. 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):1441–1446. doi: 10.1111/j.1365-2958.1992.tb00864.x. [DOI] [PubMed] [Google Scholar]
  20. Nunnari J., Walter P. Regulation of organelle biogenesis. Cell. 1996 Feb 9;84(3):389–394. doi: 10.1016/s0092-8674(00)81283-0. [DOI] [PubMed] [Google Scholar]
  21. Shamu C. E., Cox J. S., Walter P. The unfolded-protein-response pathway in yeast. Trends Cell Biol. 1994 Feb;4(2):56–60. doi: 10.1016/0962-8924(94)90011-6. [DOI] [PubMed] [Google Scholar]
  22. Shamu C. E., Walter P. Oligomerization and phosphorylation of the Ire1p kinase during intracellular signaling from the endoplasmic reticulum to the nucleus. EMBO J. 1996 Jun 17;15(12):3028–3039. [PMC free article] [PubMed] [Google Scholar]
  23. Sherman F. Getting started with yeast. Methods Enzymol. 1991;194:3–21. doi: 10.1016/0076-6879(91)94004-v. [DOI] [PubMed] [Google Scholar]
  24. Sidrauski C., Cox J. S., Walter P. tRNA ligase is required for regulated mRNA splicing in the unfolded protein response. Cell. 1996 Nov 1;87(3):405–413. doi: 10.1016/s0092-8674(00)81361-6. [DOI] [PubMed] [Google Scholar]
  25. Sweet D. J. A kinase that responds to stress. Curr Biol. 1993 Sep 1;3(9):622–624. doi: 10.1016/0960-9822(93)90014-f. [DOI] [PubMed] [Google Scholar]
  26. White M. J., Hirsch J. P., Henry S. A. The OPI1 gene of Saccharomyces cerevisiae, a negative regulator of phospholipid biosynthesis, encodes a protein containing polyglutamine tracts and a leucine zipper. J Biol Chem. 1991 Jan 15;266(2):863–872. [PubMed] [Google Scholar]
  27. Wiest D. L., Burkhardt J. K., Hester S., Hortsch M., Meyer D. I., Argon Y. Membrane biogenesis during B cell differentiation: most endoplasmic reticulum proteins are expressed coordinately. J Cell Biol. 1990 May;110(5):1501–1511. doi: 10.1083/jcb.110.5.1501. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Wright R., Basson M., D'Ari L., Rine J. 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):101–114. doi: 10.1083/jcb.107.1.101. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Molecular Biology of the Cell are provided here courtesy of American Society for Cell Biology

RESOURCES