Glycosylphosphatidylinositol (GPI)-anchored cell wall proteins (GPI-CWPs) play an important role in the structure and function of the cell wall in and other fungi. While the majority of characterized fungal GPI-anchored proteins localize to the cell wall, a subset of GPI proteins are thought to reside at the plasma membrane and not to traffic significantly to the cell wall. The amino acids immediately upstream of the site of GPI anchor addition (the site) are the primary signal determining whether a GPI protein localizes to the cell wall or to the plasma membrane. Here, evidence was found that in addition to this -proximal signal, other sequences in the protein can impact the distribution of GPI proteins between cell wall and membrane. In particular, it was found that long regions rich in serine and threonine residues (a feature of many cell wall proteins) can override the -proximal signal and redirect a model GPI plasma membrane protein to the cell wall.


Article metrics loading...

Loading full text...

Full text loading...



  1. Caras, I. W. & Weddell, G. N.(1989). Signal peptide for protein secretion directing glycophospholipid membrane anchor attachment. Science 243, 1196–1198.[CrossRef] [Google Scholar]
  2. Caras, I. W., Weddell, G. N. & Williams, S. R.(1989). Analysis of the signal for attachment of a glycophospholipid membrane anchor. J Cell Biol 108, 1387–1396.[CrossRef] [Google Scholar]
  3. Caro, L. H., Tettelin, H., Vossen, J. H., Ram, A. F., van den Ende, H. & Klis, F. M.(1997). In silico identification of glycosyl-phosphatidylinositol-anchored plasma-membrane and cell wall proteins of Saccharomyces cerevisiae. Yeast 13, 1477–1489.[CrossRef] [Google Scholar]
  4. Cormack, B. P., Ghori, N. & Falkow, S.(1999). An adhesin of the yeast pathogen Candida glabrata mediating adherence to human epithelial cells. Science 285, 578–582.[CrossRef] [Google Scholar]
  5. De Groot, P. W., Hellingwerf, K. J. & Klis, F. M.(2003). Genome-wide identification of fungal GPI proteins. Yeast 20, 781–796.[CrossRef] [Google Scholar]
  6. De Sampaio, G., Bourdineaud, J. P. & Lauquin, G. J.(1999). A constitutive role for GPI anchors in Saccharomyces cerevisiae: cell wall targeting. Mol Microbiol 34, 247–256.[CrossRef] [Google Scholar]
  7. Doering, T. L. & Schekman, R.(1996). GPI anchor attachment is required for Gas1p transport from the endoplasmic reticulum in COP II vesicles. EMBO J 15, 182–191. [Google Scholar]
  8. Eisenhaber, B., Schneider, G., Wildpaner, M. & Eisenhaber, F.(2004). A sensitive predictor for potential GPI lipid modification sites in fungal protein sequences and its application to genome-wide studies for Aspergillus nidulans, Candida albicans, Neurospora crassa, Saccharomyces cerevisiae and Schizosaccharomyces pombe. J Mol Biol 337, 243–253.[CrossRef] [Google Scholar]
  9. Frieman, M. B. & Cormack, B. P.(2003). The omega-site sequence of glycosylphosphatidylinositol-anchored proteins in Saccharomyces cerevisiae can determine distribution between the membrane and the cell wall. Mol Microbiol 50, 883–896.[CrossRef] [Google Scholar]
  10. Frieman, M. B., McCaffery, J. M. & Cormack, B. P.(2002). Modular domain structure in the Candida glabrata adhesin Epa1p, a beta1,6 glucan-cross-linked cell wall protein. Mol Microbiol 46, 479–492.[CrossRef] [Google Scholar]
  11. Gietz, D., St Jean, A., Woods, R. A. & Schiestl, R. H.(1992). Improved method for high efficiency transformation of intact yeast cells. Nucleic Acids Res 20, 1425.[CrossRef] [Google Scholar]
  12. Hamada, K., Terashima, H., Arisawa, M. & Kitada, K.(1998). Amino acid sequence requirement for efficient incorporation of glycosylphosphatidylinositol-associated proteins into the cell wall of Saccharomyces cerevisiae. J Biol Chem 273, 26946–26953.[CrossRef] [Google Scholar]
  13. Hamada, K., Terashima, H., Arisawa, M., Yabuki, N. & Kitada, K.(1999). Amino acid residues in the omega-minus region participate in cellular localization of yeast glycosylphosphatidylinositol-attached proteins. J Bacteriol 181, 3886–3889. [Google Scholar]
  14. Hoyer, L. L., Fundyga, R., Hecht, J. E., Kapteyn, J. C., Klis, F. M. & Arnold, J.(2001). Characterization of agglutinin-like sequence genes from non-albicans Candida and phylogenetic analysis of the ALS family. Genetics 157, 1555–1567. [Google Scholar]
  15. Jentoft, N.(1990). Why are proteins O-glycosylated? Trends Biochem Sci 15, 291–294.[CrossRef] [Google Scholar]
  16. Kapteyn, J. C., Montijn, R. C., Dijkgraaf, G. J. & Klis, F. M.(1994). Identification of beta-1,6-glucosylated cell wall proteins in yeast and hyphal forms of Candida albicans. Eur J Cell Biol 65, 402–407. [Google Scholar]
  17. Klis, F. M., Caro, L. H., Vossen, J. H., Kapteyn, J. C., Ram, A. F., Montijn, R. C., Van Berkel, M. A. & Van den Ende, H.(1997). Identification and characterization of a major building block in the cell wall of Saccharomyces cerevisiae. Biochem Soc Trans 25, 856–860. [Google Scholar]
  18. Lo, W. S. & Dranginis, A. M.(1996). FLO11, a yeast gene related to the STA genes, encodes a novel cell surface flocculin. J Bacteriol 178, 7144–7151. [Google Scholar]
  19. Lu, C. F., Kurjan, J. & Lipke, P. N.(1994). A pathway for cell wall anchorage of Saccharomyces cerevisiae alpha-agglutinin. Mol Cell Biol 14, 4825–4833. [Google Scholar]
  20. Moran, P. & Caras, I. W.(1991). A nonfunctional sequence converted to a signal for glycophosphatidylinositol membrane anchor attachment. J Cell Biol 115, 329–336.[CrossRef] [Google Scholar]
  21. Philip, B. & Levin, D. E.(2001). Wsc1 and Mid2 are cell surface sensors for cell wall integrity signaling that act through Rom2, a guanine nucleotide exchange factor for Rho1. Mol Cell Biol 21, 271–280.[CrossRef] [Google Scholar]
  22. Popolo, L. & Vai, M.(1999). The Gas1 glycoprotein, a putative wall polymer cross-linker. Biochim Biophys Acta 1426, 385–400.[CrossRef] [Google Scholar]
  23. Sherman, F., Fink, G. R. & Hicks, J. B.(1986).Methods in Yeast Genetics. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory.
  24. Stratford, M.(1994). Another brick in the wall? Recent developments concerning the yeast cell envelope. Yeast 10, 1741–1752.[CrossRef] [Google Scholar]
  25. Sundstrom, P.(2002). Adhesion in Candida spp. Cell Microbiol 4, 461–469.[CrossRef] [Google Scholar]
  26. Terashima, H., Hamada, K. & Kitada, K.(2003). The localization change of Ybr078w/Ecm33, a yeast GPI-associated protein, from the plasma membrane to the cell wall, affecting the cellular function. FEMS Microbiol Lett 218, 175–180.[CrossRef] [Google Scholar]
  27. Teunissen, A. W., Holub, E., van der Hucht, J., van den Berg, J. A. & Steensma, H. Y.(1993). Sequence of the open reading frame of the FLO1 gene from Saccharomyces cerevisiae. Yeast 9, 423–427.[CrossRef] [Google Scholar]
  28. van der Vaart, J. M., Caro, L. H., Chapman, J. W., Klis, F. M. & Verrips, C. T.(1995). Identification of three mannoproteins in the cell wall of Saccharomyces cerevisiae. J Bacteriol 177, 3104–3110. [Google Scholar]
  29. Watari, J., Takata, Y., Ogawa, M. & 7 other authors(1994). Molecular cloning and analysis of the yeast flocculation gene FLO1. Yeast 10, 211–225.[CrossRef] [Google Scholar]

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error