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. 1997 Apr 15;16(8):1832–1841. doi: 10.1093/emboj/16.8.1832

Transmembrane domain-dependent sorting of proteins to the ER and plasma membrane in yeast.

J C Rayner 1, H R Pelham 1
PMCID: PMC1169786  PMID: 9155009

Abstract

Sorting of membrane proteins between compartments of the secretory pathway is mediated in part by their transmembrane domains (TMDs). In animal cells, TMD length is a major factor in Golgi retention. In yeast, the role of TMD signals is less clear; it has been proposed that membrane proteins travel by default to the vacuole, and are prevented from doing so by cytoplasmic signals. We have investigated the targeting of the yeast endoplasmic reticulum (ER) t-SNARE Ufe1p. We show that the amino acid sequence of the Ufe1p TMD is important for both function and ER targeting, and that the requirements for each are distinct. Targeting is independent of Rer1p, the only candidate sorting receptor for TMD sequences currently known. Lengthening the Ufe1p TMD allows transport along the secretory pathway to the vacuole or plasma membrane. The choice between these destinations is determined by the length and composition of the TMD, but not by its precise sequence. A longer TMD is required to reach the plasma membrane in yeast than in animal cells, and shorter TMDs direct proteins to the vacuole. TMD-based sorting is therefore a general feature of the yeast secretory pathway, but occurs by different mechanisms at different points.

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Selected References

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

  1. Banfield D. K., Lewis M. J., Pelham H. R. A SNARE-like protein required for traffic through the Golgi complex. Nature. 1995 Jun 29;375(6534):806–809. doi: 10.1038/375806a0. [DOI] [PubMed] [Google Scholar]
  2. Becherer K. A., Rieder S. E., Emr S. D., Jones E. W. Novel syntaxin homologue, Pep12p, required for the sorting of lumenal hydrolases to the lysosome-like vacuole in yeast. Mol Biol Cell. 1996 Apr;7(4):579–594. doi: 10.1091/mbc.7.4.579. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Boehm J., Ulrich H. D., Ossig R., Schmitt H. D. Kex2-dependent invertase secretion as a tool to study the targeting of transmembrane proteins which are involved in ER-->Golgi transport in yeast. EMBO J. 1994 Aug 15;13(16):3696–3710. doi: 10.1002/j.1460-2075.1994.tb06679.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bowser R., Novick P. Sec15 protein, an essential component of the exocytotic apparatus, is associated with the plasma membrane and with a soluble 19.5S particle. J Cell Biol. 1991 Mar;112(6):1117–1131. doi: 10.1083/jcb.112.6.1117. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bretscher M. S., Munro S. Cholesterol and the Golgi apparatus. Science. 1993 Sep 3;261(5126):1280–1281. doi: 10.1126/science.8362242. [DOI] [PubMed] [Google Scholar]
  6. Chalfie M., Tu Y., Euskirchen G., Ward W. W., Prasher D. C. Green fluorescent protein as a marker for gene expression. Science. 1994 Feb 11;263(5148):802–805. doi: 10.1126/science.8303295. [DOI] [PubMed] [Google Scholar]
  7. Chapman R. E., Munro S. The functioning of the yeast Golgi apparatus requires an ER protein encoded by ANP1, a member of a new family of genes affecting the secretory pathway. EMBO J. 1994 Oct 17;13(20):4896–4907. doi: 10.1002/j.1460-2075.1994.tb06817.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Evan G. I., Lewis G. K., Ramsay G., Bishop J. M. Isolation of monoclonal antibodies specific for human c-myc proto-oncogene product. Mol Cell Biol. 1985 Dec;5(12):3610–3616. doi: 10.1128/mcb.5.12.3610. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Graham T. R., Krasnov V. A. Sorting of yeast alpha 1,3 mannosyltransferase is mediated by a lumenal domain interaction, and a transmembrane domain signal that can confer clathrin-dependent Golgi localization to a secreted protein. Mol Biol Cell. 1995 Jul;6(7):809–824. doi: 10.1091/mbc.6.7.809. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. 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]
  11. Hennecke S., Cosson P. Role of transmembrane domains in assembly and intracellular transport of the CD8 molecule. J Biol Chem. 1993 Dec 15;268(35):26607–26612. [PubMed] [Google Scholar]
  12. Kee Y., Lin R. C., Hsu S. C., Scheller R. H. Distinct domains of syntaxin are required for synaptic vesicle fusion complex formation and dissociation. Neuron. 1995 May;14(5):991–998. doi: 10.1016/0896-6273(95)90337-2. [DOI] [PubMed] [Google Scholar]
  13. Lewis M. J., Pelham H. R. SNARE-mediated retrograde traffic from the Golgi complex to the endoplasmic reticulum. Cell. 1996 Apr 19;85(2):205–215. doi: 10.1016/s0092-8674(00)81097-1. [DOI] [PubMed] [Google Scholar]
  14. Lussier M., Sdicu A. M., Ketela T., Bussey H. Localization and targeting of the Saccharomyces cerevisiae Kre2p/Mnt1p alpha 1,2-mannosyltransferase to a medial-Golgi compartment. J Cell Biol. 1995 Nov;131(4):913–927. doi: 10.1083/jcb.131.4.913. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Munro S. An investigation of the role of transmembrane domains in Golgi protein retention. EMBO J. 1995 Oct 2;14(19):4695–4704. doi: 10.1002/j.1460-2075.1995.tb00151.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Munro S. Sequences within and adjacent to the transmembrane segment of alpha-2,6-sialyltransferase specify Golgi retention. EMBO J. 1991 Dec;10(12):3577–3588. doi: 10.1002/j.1460-2075.1991.tb04924.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Nilsson T., Lucocq J. M., Mackay D., Warren G. The membrane spanning domain of beta-1,4-galactosyltransferase specifies trans Golgi localization. EMBO J. 1991 Dec;10(12):3567–3575. doi: 10.1002/j.1460-2075.1991.tb04923.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Nothwehr S. F., Roberts C. J., Stevens T. H. Membrane protein retention in the yeast Golgi apparatus: dipeptidyl aminopeptidase A is retained by a cytoplasmic signal containing aromatic residues. J Cell Biol. 1993 Jun;121(6):1197–1209. doi: 10.1083/jcb.121.6.1197. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Pedrazzini E., Villa A., Borgese N. A mutant cytochrome b5 with a lengthened membrane anchor escapes from the endoplasmic reticulum and reaches the plasma membrane. Proc Natl Acad Sci U S A. 1996 Apr 30;93(9):4207–4212. doi: 10.1073/pnas.93.9.4207. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Ponnambalam S., Rabouille C., Luzio J. P., Nilsson T., Warren G. The TGN38 glycoprotein contains two non-overlapping signals that mediate localization to the trans-Golgi network. J Cell Biol. 1994 Apr;125(2):253–268. doi: 10.1083/jcb.125.2.253. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Raymond C. K., Howald-Stevenson I., Vater C. A., Stevens T. H. Morphological classification of the yeast vacuolar protein sorting mutants: evidence for a prevacuolar compartment in class E vps mutants. Mol Biol Cell. 1992 Dec;3(12):1389–1402. doi: 10.1091/mbc.3.12.1389. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Reth M., Hombach J., Wienands J., Campbell K. S., Chien N., Justement L. B., Cambier J. C. The B-cell antigen receptor complex. Immunol Today. 1991 Jun;12(6):196–201. doi: 10.1016/0167-5699(91)90053-V. [DOI] [PubMed] [Google Scholar]
  23. 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]
  24. Sato M., Sato K., Nakano A. Endoplasmic reticulum localization of Sec12p is achieved by two mechanisms: Rer1p-dependent retrieval that requires the transmembrane domain and Rer1p-independent retention that involves the cytoplasmic domain. J Cell Biol. 1996 Jul;134(2):279–293. doi: 10.1083/jcb.134.2.279. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. 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]
  26. Swift A. M., Machamer C. E. A Golgi retention signal in a membrane-spanning domain of coronavirus E1 protein. J Cell Biol. 1991 Oct;115(1):19–30. doi: 10.1083/jcb.115.1.19. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Söllner T., Bennett M. K., Whiteheart S. W., Scheller R. H., Rothman J. E. A protein assembly-disassembly pathway in vitro that may correspond to sequential steps of synaptic vesicle docking, activation, and fusion. Cell. 1993 Nov 5;75(3):409–418. doi: 10.1016/0092-8674(93)90376-2. [DOI] [PubMed] [Google Scholar]
  28. Söllner T., Whiteheart S. W., Brunner M., Erdjument-Bromage H., Geromanos S., Tempst P., Rothman J. E. SNAP receptors implicated in vesicle targeting and fusion. Nature. 1993 Mar 25;362(6418):318–324. doi: 10.1038/362318a0. [DOI] [PubMed] [Google Scholar]
  29. Wilcox C. A., Redding K., Wright R., Fuller R. S. Mutation of a tyrosine localization signal in the cytosolic tail of yeast Kex2 protease disrupts Golgi retention and results in default transport to the vacuole. Mol Biol Cell. 1992 Dec;3(12):1353–1371. doi: 10.1091/mbc.3.12.1353. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Zinser E., Paltauf F., Daum G. Sterol composition of yeast organelle membranes and subcellular distribution of enzymes involved in sterol metabolism. J Bacteriol. 1993 May;175(10):2853–2858. doi: 10.1128/jb.175.10.2853-2858.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Zinser E., Sperka-Gottlieb C. D., Fasch E. V., Kohlwein S. D., Paltauf F., Daum G. Phospholipid synthesis and lipid composition of subcellular membranes in the unicellular eukaryote Saccharomyces cerevisiae. J Bacteriol. 1991 Mar;173(6):2026–2034. doi: 10.1128/jb.173.6.2026-2034.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]

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