Mannosylphosphate Transfer to Yeast Mannan

Mannoproteins located in the outermost layer of yeast cell wall determine the wall's porosity and thereby regulate leakage of proteins from the periplasmic space and entrance of macromolecules from the environment. In several yeasts, including Saccharomyces cerevisiae, the glycan portion of mannoproteins is composed not only of neutral oligosaccharides containing mannose and N-acetylglucosamine, but also of acidic oligosaccharides containing mannosylphosphate. The mannosylphosphate residues confer a net negative charge on the cell wall, and so change the properties and environment of the cell surface. Progress on mannosylphosphorylation and its regulation in S. cerevisiae is summarized. Two genes required for mannosylphosphate transfer, MNN4 and MNN6, have been cloned, and a functional analysis of these genes suggests a mechanism for mannosylphosphate transfer. Possible functions for mannosylphosphate transfer in yeast are also discussed. These include supply of GMP for sugar nucleotide transport in the Golgi, cross-linking of mannoproteins to beta-glucan, and a cellular stress response to environmental changes. Glycans in pathogenic yeast and protozoa are also modified with mannosylphosphate, and the potential contribution of this modification to the pathogenicity of these organisms is evaluated.