Trends in Microbiology
Non-conventional protein secretionin yeast
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.
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