Trends in Microbiology
Volume 14, Issue 1, January 2006, Pages 15-21
Journal home page for Trends in Microbiology

Non-conventional protein secretionin yeast

https://doi.org/10.1016/j.tim.2005.11.009Get rights and content

Many proteins are transported to the cell surface of Saccharomyces cerevisiae and Candida albicans to be either integrated into the cell-wall structure or exported to the external medium. Secretion of many of these proteins through the classical endoplasmic reticulum–Golgi pathway is driven by a canonical N-terminal signal peptide. However, several surface proteins lacking this motif can also access the cell surface and remain loosely bound to the wall. The previous identification of these secretion-signal-less proteins in the cytoplasm as proteins that function as glycolytic enzymes, chaperones, translation factors and others suggests that they could be ‘moonlighting’ (multifunctional) proteins. The accumulated evidence indicates that mechanisms of secretion other than the endoplasmic reticulum–Golgi pathway drive these proteins outside the plasma membrane. The relevance of these secretion-signal-less proteins in virulence and cell-wall dynamics warrants further characterization of alternative secretion in yeasts.

Section snippets

Towards an integrated view of cell-wall biogenesis

Yeast cells have a thick wall that maintains cell shape, protects against osmotic stress and requires modification for both oval and dimorphic cell growth. The polysaccharide scaffold that strengthens the cell wall consists of a flexible network of branched 1,3-β-glucan, to which 1,6-β-glucan and chitin are attached by their reducing ends, with some chitin attached directly to 1,6-β-glucan [1]. Approximately 20% of the Saccharomyces cerevisiae genome is required for cell-wall biogenesis, which

Proteins lacking N-terminal secretion signal peptides at the yeast cell surface

Evidence of proteins at the yeast cell surface that lack N-terminal signal peptides was initially provided by morphological, biochemical and genetic studies. The existence of many such proteins has subsequently been demonstrated by proteomic approaches (Table 1). C. albicans and S. cerevisiae share 11 signal-less proteins in common; a further 26 have been described only in the former, compared with five identified only in the latter yeast species. Many of the surface proteins lacking the

Export of proteins that lack an N-terminal secretion signal

A genetic study of the S. cerevisiae Hsp70 protein chaperone family demonstrated that the presence of Hsp70 at the cell wall was attributable to either Ssa1p or Ssa2p chaperone family members. In the strain missing both of these proteins (in which Ssa3p and, particularly, Ssa4p carry out the family function) Hsp70 was detectable in the cytoplasm but not in cell-wall extracts. The extracts were also missing additional proteins, which perhaps required the translocation function of the missing

Alternative secretion proteins as virulence factors of microbes

The connection between signal-less non-conventional surface proteins with microbial virulence reinforces interest in the phenomenon of alternative secretion. In C. albicans, identification of plasminogen-binding surface proteins revealed several enzymes and a transcription elongation factor [23]. For example, enolase interacts with plasminogen and plasmin, thereby potentially contributing to tissue invasion by C. albicans [24]. The immune response against candidal enolase is relevant in

Potential routes for export

The diversity of non-conventional cell-surface proteins in yeast does not enable postulation of a single mechanism for channelling these proteins to the cell surface. However, several possibilities can be envisaged from observations made in yeasts and other organisms (Figure 2). Data from S. cerevisiae indicate that the ATP-binding cassette transporter is a potential driver for protein export. In addition, non-classical export (NCE) genes NCE101 and NCE102 are related to non-classical export of

Concluding remarks and future perspectives

The observations reviewed here add complexity to the current understanding of structures located outside the plasma membrane. As discussed, surprising findings such as alternative secretion require more than the normal standard of verification. The possibility of exporting proteins that lack the canonical N-terminal secretion signal is widespread (e.g. in mammalian cells, bacteria, lower eukaryotes and protozoa) – it seems to be a general phenomenon that could operate by several routes and

Acknowledgements

This work was supported by project grants BIO-2003–00030 from the Comisión Interministerial de Ciencia y Tecnología (CICYT) and from Fundación Ramón Areces, Spain. C.N. is Director of the Merck, Sharp and Dohme (MSD) Special Chair in Genomics and Proteomics. We thank Aida Pitarch for the design of the figures and Lucía Monteoliva for helpful discussions.

References (51)

  • R. Sijbrandi

    Characterization of an iron-regulated alpha-enolase of Bacteroides fragilis

    Microbes Infect.

    (2005)
  • X.S. Li

    Candida albicans Ssa1/2p is the cell envelope binding protein for human salivary histatin 5

    J. Biol. Chem.

    (2003)
  • F.M. Klis

    Molecular organization of the cell wall of Candida albicans

    Med. Mycol.

    (2001)
  • P.W.J. de Groot

    A genomic approach for the identification and classification of genes involved in cell wall formation and its regulation in Saccharomyces cerevisiae

    Comp. Funct. Genomics

    (2001)
  • P.W. de Groot

    Genome-wide identification of fungal GPI proteins

    Yeast

    (2003)
  • J.C. Kapteyn

    The cell wall architecture of Candida albicans wild-type cells and cell wall-defective mutants

    Mol. Microbiol.

    (2000)
  • J.R. Naglik

    Candida albicans secreted aspartyl proteinases in virulence and pathogenesis

    Microbiol. Mol. Biol. Rev.

    (2003)
  • D. Gozalbo

    The cell wall-associated glyceraldehyde-3-phosphate dehydrogenase of Candida albicans is also a fibronectin and laminin binding protein

    Infect. Immun.

    (1998)
  • P. Eroles

    The highly immunogenic enolase and Hsp70p are adventitious Candida albicans cell wall proteins

    Microbiol.

    (1997)
  • C.J. Jeffery

    Multifunctional proteins: examples of gene sharing

    Ann. Med.

    (2003)
  • M. Pardo

    Two-dimensional analysis of proteins secreted by Saccharomyces cerevisiae regenerating protoplasts: a novel approach to study the cell wall

    Yeast

    (1999)
  • L. Angiolella

    Identification of major glucan-associated cell wall proteins of Candida albicans and their role in fluconazole resistance

    Antimicrob. Agents Chemother.

    (2002)
  • V. Mrsa

    Specific labelling of cell wall proteins by biotinylation. Identification of four covalently linked O-mannosylated proteins of Saccharomyces cerevisiae

    Yeast

    (1997)
  • J.L. Lopez-Ribot et al.

    Members of the Hsp70 family of proteins in the cell wall of Saccharomyces cerevisiae

    J. Bacteriol.

    (1996)
  • M.L. Delgado

    Candida albicans TDH3 gene promotes secretion of internal invertase when expressed in Saccharomyces cerevisiae as a glyceraldehyde-3-phosphate dehydrogenase-invertase fusion protein

    Yeast

    (2003)
  • Cited by (176)

    • Exploring the secretome of Corynebacterium glutamicum ATCC 13032

      2024, Frontiers in Bioengineering and Biotechnology
    View all citing articles on Scopus
    View full text