Abstract
The yeast SEC12 gene product (Sec12p) is an integral membrane protein required for the protein transport from the endoplasmic reticulum (ER) to the Golgi apparatus. Although this protein is almost exclusively localized in the ER, a significant fraction of Sec12p is modified by an enzyme that resides in the early compartment of the Golgi apparatus, suggesting that Sec12p is cycling between the ER and the early Golgi. We have taken a genetic approach to investigate the retention mechanism of Sec12p. Analysis of mutants that are defective in the retention of the Sec12-Mf alpha 1 fusion protein in the early secretory compartments has identified a gene, RER1. A recessive mutation in RER1 causes mislocalization of the authentic Sec12p as well as two different Sec12 fusion proteins to the late Golgi apparatus and even to the cell surface. However, the rer1 mutant is not defective in the retention of an ER-resident soluble protein, BiP, suggesting that soluble and membrane proteins are retained in the ER by distinct mechanisms.
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- Chan R. K., Otte C. A. Isolation and genetic analysis of Saccharomyces cerevisiae mutants supersensitive to G1 arrest by a factor and alpha factor pheromones. Mol Cell Biol. 1982 Jan;2(1):11–20. doi: 10.1128/mcb.2.1.11. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Dean N., Pelham H. R. Recycling of proteins from the Golgi compartment to the ER in yeast. J Cell Biol. 1990 Aug;111(2):369–377. doi: 10.1083/jcb.111.2.369. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Emr S. D., Vassarotti A., Garrett J., Geller B. L., Takeda M., Douglas M. G. The amino terminus of the yeast F1-ATPase beta-subunit precursor functions as a mitochondrial import signal. J Cell Biol. 1986 Feb;102(2):523–533. doi: 10.1083/jcb.102.2.523. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Franzusoff A., Schekman R. Functional compartments of the yeast Golgi apparatus are defined by the sec7 mutation. EMBO J. 1989 Sep;8(9):2695–2702. doi: 10.1002/j.1460-2075.1989.tb08410.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Goldstein A., Lampen J. O. Beta-D-fructofuranoside fructohydrolase from yeast. Methods Enzymol. 1975;42:504–511. doi: 10.1016/0076-6879(75)42159-0. [DOI] [PubMed] [Google Scholar]
- Graham T. R., Emr S. D. Compartmental organization of Golgi-specific protein modification and vacuolar protein sorting events defined in a yeast sec18 (NSF) mutant. J Cell Biol. 1991 Jul;114(2):207–218. doi: 10.1083/jcb.114.2.207. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hansen W., Garcia P. D., Walter P. In vitro protein translocation across the yeast endoplasmic reticulum: ATP-dependent posttranslational translocation of the prepro-alpha-factor. Cell. 1986 May 9;45(3):397–406. doi: 10.1016/0092-8674(86)90325-9. [DOI] [PubMed] [Google Scholar]
- Hardwick K. G., Boothroyd J. C., Rudner A. D., Pelham H. R. Genes that allow yeast cells to grow in the absence of the HDEL receptor. EMBO J. 1992 Nov;11(11):4187–4195. doi: 10.1002/j.1460-2075.1992.tb05512.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hardwick K. G., Lewis M. J., Semenza J., Dean N., Pelham H. R. ERD1, a yeast gene required for the retention of luminal endoplasmic reticulum proteins, affects glycoprotein processing in the Golgi apparatus. EMBO J. 1990 Mar;9(3):623–630. doi: 10.1002/j.1460-2075.1990.tb08154.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hardwick K. G., Pelham H. R. ERS1 a seven transmembrane domain protein from Saccharomyces cerevisiae. Nucleic Acids Res. 1990 Apr 25;18(8):2177–2177. doi: 10.1093/nar/18.8.2177. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hardwick K. G., Pelham H. R. SED5 encodes a 39-kD integral membrane protein required for vesicular transport between the ER and the Golgi complex. J Cell Biol. 1992 Nov;119(3):513–521. doi: 10.1083/jcb.119.3.513. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hsu V. W., Yuan L. C., Nuchtern J. G., Lippincott-Schwartz J., Hammerling G. J., Klausner R. D. A recycling pathway between the endoplasmic reticulum and the Golgi apparatus for retention of unassembled MHC class I molecules. Nature. 1991 Aug 1;352(6334):441–444. doi: 10.1038/352441a0. [DOI] [PubMed] [Google Scholar]
- Jackson M. R., Nilsson T., Peterson P. A. Identification of a consensus motif for retention of transmembrane proteins in the endoplasmic reticulum. EMBO J. 1990 Oct;9(10):3153–3162. doi: 10.1002/j.1460-2075.1990.tb07513.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kato N., Sahm H., Schütte H., Wagner F. Purification and properties of glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase from a methanol-utilizing yeast, Candida boidinii. Biochim Biophys Acta. 1979 Jan 12;566(1):1–11. doi: 10.1016/0005-2744(79)90242-0. [DOI] [PubMed] [Google Scholar]
- Kurjan J., Herskowitz I. Structure of a yeast pheromone gene (MF alpha): a putative alpha-factor precursor contains four tandem copies of mature alpha-factor. Cell. 1982 Oct;30(3):933–943. doi: 10.1016/0092-8674(82)90298-7. [DOI] [PubMed] [Google Scholar]
- Lewis M. J., Pelham H. R. A human homologue of the yeast HDEL receptor. Nature. 1990 Nov 8;348(6297):162–163. doi: 10.1038/348162a0. [DOI] [PubMed] [Google Scholar]
- Lewis M. J., Pelham H. R. Ligand-induced redistribution of a human KDEL receptor from the Golgi complex to the endoplasmic reticulum. Cell. 1992 Jan 24;68(2):353–364. doi: 10.1016/0092-8674(92)90476-s. [DOI] [PubMed] [Google Scholar]
- Lewis M. J., Sweet D. J., Pelham H. R. The ERD2 gene determines the specificity of the luminal ER protein retention system. Cell. 1990 Jun 29;61(7):1359–1363. doi: 10.1016/0092-8674(90)90699-f. [DOI] [PubMed] [Google Scholar]
- Munro S., Pelham H. R. A C-terminal signal prevents secretion of luminal ER proteins. Cell. 1987 Mar 13;48(5):899–907. doi: 10.1016/0092-8674(87)90086-9. [DOI] [PubMed] [Google Scholar]
- Nakano A., Brada D., Schekman R. A membrane glycoprotein, Sec12p, required for protein transport from the endoplasmic reticulum to the Golgi apparatus in yeast. J Cell Biol. 1988 Sep;107(3):851–863. doi: 10.1083/jcb.107.3.851. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Nakańo A., Muramatsu M. A novel GTP-binding protein, Sar1p, is involved in transport from the endoplasmic reticulum to the Golgi apparatus. J Cell Biol. 1989 Dec;109(6 Pt 1):2677–2691. doi: 10.1083/jcb.109.6.2677. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Novick P., Field C., Schekman R. Identification of 23 complementation groups required for post-translational events in the yeast secretory pathway. Cell. 1980 Aug;21(1):205–215. doi: 10.1016/0092-8674(80)90128-2. [DOI] [PubMed] [Google Scholar]
- Oliver S. G., van der Aart Q. J., Agostoni-Carbone M. L., Aigle M., Alberghina L., Alexandraki D., Antoine G., Anwar R., Ballesta J. P., Benit P. The complete DNA sequence of yeast chromosome III. Nature. 1992 May 7;357(6373):38–46. doi: 10.1038/357038a0. [DOI] [PubMed] [Google Scholar]
- Pelham H. R. Evidence that luminal ER proteins are sorted from secreted proteins in a post-ER compartment. EMBO J. 1988 Apr;7(4):913–918. doi: 10.1002/j.1460-2075.1988.tb02896.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Pelham H. R., Hardwick K. G., Lewis M. J. Sorting of soluble ER proteins in yeast. EMBO J. 1988 Jun;7(6):1757–1762. doi: 10.1002/j.1460-2075.1988.tb03005.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Qadota H., Ishii I., Fujiyama A., Ohya Y., Anraku Y. RHO gene products, putative small GTP-binding proteins, are important for activation of the CAL1/CDC43 gene product, a protein geranylgeranyltransferase in Saccharomyces cerevisiae. Yeast. 1992 Sep;8(9):735–741. doi: 10.1002/yea.320080906. [DOI] [PubMed] [Google Scholar]
- Redding K., Holcomb C., Fuller R. S. Immunolocalization of Kex2 protease identifies a putative late Golgi compartment in the yeast Saccharomyces cerevisiae. J Cell Biol. 1991 May;113(3):527–538. doi: 10.1083/jcb.113.3.527. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rexach M. F., Schekman R. W. Distinct biochemical requirements for the budding, targeting, and fusion of ER-derived transport vesicles. J Cell Biol. 1991 Jul;114(2):219–229. doi: 10.1083/jcb.114.2.219. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Roberts C. J., Nothwehr S. F., Stevens T. H. Membrane protein sorting in the yeast secretory pathway: evidence that the vacuole may be the default compartment. J Cell Biol. 1992 Oct;119(1):69–83. doi: 10.1083/jcb.119.1.69. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Semenza J. C., Hardwick K. G., Dean N., Pelham H. R. ERD2, a yeast gene required for the receptor-mediated retrieval of luminal ER proteins from the secretory pathway. Cell. 1990 Jun 29;61(7):1349–1357. doi: 10.1016/0092-8674(90)90698-e. [DOI] [PubMed] [Google Scholar]
- Sikorski R. S., Hieter P. 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. doi: 10.1093/genetics/122.1.19. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sprague G. F., Jr Assay of yeast mating reaction. Methods Enzymol. 1991;194:77–93. doi: 10.1016/0076-6879(91)94008-z. [DOI] [PubMed] [Google Scholar]
- Wickerham L. J. A Critical Evaluation of the Nitrogen Assimilation Tests Commonly Used in the Classification of Yeasts. J Bacteriol. 1946 Sep;52(3):293–301. [PMC free article] [PubMed] [Google Scholar]
- d'Enfert C., Barlowe C., Nishikawa S., Nakano A., Schekman R. Structural and functional dissection of a membrane glycoprotein required for vesicle budding from the endoplasmic reticulum. Mol Cell Biol. 1991 Nov;11(11):5727–5734. doi: 10.1128/mcb.11.11.5727. [DOI] [PMC free article] [PubMed] [Google Scholar]
- te Heesen S., Janetzky B., Lehle L., Aebi M. The yeast WBP1 is essential for oligosaccharyl transferase activity in vivo and in vitro. EMBO J. 1992 Jun;11(6):2071–2075. doi: 10.1002/j.1460-2075.1992.tb05265.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- te Heesen S., Rauhut R., Aebersold R., Abelson J., Aebi M., Clark M. W. An essential 45 kDa yeast transmembrane protein reacts with anti-nuclear pore antibodies: purification of the protein, immunolocalization and cloning of the gene. Eur J Cell Biol. 1991 Oct;56(1):8–18. [PubMed] [Google Scholar]