The Yeast Cell Wall and Septum as Paradigms of Cell Growth and Morphogenesis

Abstract

CSII, CSIII, chitin synthase I, II, and III, respectively endoplasmic reticulum. Roman numerals are used to designate the enzymes because, in addition to the putative catalytic moieties, i.e. Chs1p, Chs2p and Chs3p, they may contain activators (such as Chs4p for CSIII) and perhaps proteins needed to guide the newly formed polysaccharide through the plasma membrane Fungal cells, like their bacterial and plant counterparts but unlike animal cells, are encased in a sturdy shell, the cell wall, which is essential for their survival. Fungal cells have a very high turgor pressure, and even a minor chink in the cell wall structure can lead to bursting and death (1Cabib E. Sburlati A. Bowers B. Silverman S.J. J. Cell Biol. 1989; 108: 1665-1672Crossref PubMed Scopus (138) Google Scholar). Yet, because the cell wall is external to the cell, it must grow with it and endure all the changes that the cell undergoes during the division cycle. To ensure the continuous integrity of the cell wall without interfering with its plasticity and constant growth, elaborate control mechanisms must be operating, which need to be strictly coordinated with those governing the cell cycle. There are two major reasons for studying the fungal cell wall and its specialized structure for cell division, the septum. 1) Of theoretical interest is that the cell wall, because it imparts shape to the cell in a constantly changing pattern and because of its relatively simple composition, serves as a good model for morphogenesis at the molecular level. 2) Another reason, of an applied nature, is that cell wall synthesis is an attractive target for antifungal agents because it is unique to the pathogen. Because of the versatility of budding yeast for biochemical and genetic studies, the most comprehensive body of work on fungal cell walls has been carried out with this organism. Therefore, this review will deal specifically with Saccharomyces cerevisiae. The yeast cell wall consists mainly of polysaccharides made up of three sugars, glucose, mannose, and N-acetylglucosamine. One of the glucose polysaccharides, β(1→3)glucan, is the major structural component of the wall. Another, β(1→6)glucan, is relatively minor in amount but very important for cross-linking (see below). The mannose polysaccharides are linked to proteins to form a mannoprotein layer mainly localized at the external surface and acting as a filter for large molecular weight materials (2Zlotnik H. Fernández M.P. Bowers B. Cabib E. J. Bacteriol. 1984; 159: 1018-1026Crossref PubMed Google Scholar). Finally, the small amount of GlcNAc present in the wall (1–3%) is in the β(1→4)-linked linear polysaccharide chitin, which is mostly concentrated in the septal region although some is dispersed throughout the wall. Despite its small quantity, chitin is essential for yeast survival (3Shaw J.A. Mol P.C. Bowers B. Silverman S.J. Valdivieso M.H. Durán A. Cabib E. J. Cell Biol. 1991; 114: 111-123Crossref PubMed Scopus (361) Google Scholar), probably because of its central role in septation. An early indication that the yeast cell wall components are attached to each other by covalent linkages was that mannoproteins, insoluble in native walls, became soluble in water after digestion of the walls with an endo-β(1→3)-glucanase (2Zlotnik H. Fernández M.P. Bowers B. Cabib E. J. Bacteriol. 1984; 159: 1018-1026Crossref PubMed Google Scholar). This suggested a direct or indirect attachment between β(1→3)glucan and mannoproteins. The first fully characterized linkage between cell wall components was the β(1→4) bond between the reducing terminal GlcNAc of a chitin chain and the nonreducing terminal glucose of β(1→3)glucan (Fig.1 A) (4Kollár R. Petráková E. Ashwell G. Robbins P.W. Cabib E. J. Biol. Chem. 1995; 270: 1170-1178Abstract Full Text Full Text PDF PubMed Scopus (236) Google Scholar). Other studies revealed an association between mannoproteins, β(1→6)glucan and β(1→3)glucan (5Kapteyn J.C. Montijn R.C. Vink E. de la Cruz J. Llobell A. Shimoi H. Lipke P. Klis F.M. Glycobiology. 1996; 6: 337-345Crossref PubMed Scopus (223) Google Scholar). Finally, the linkages of a complex including those three components plus chitin were identified and partially characterized (Fig. 1 B) (6Kollár R. Reinhold B.B. Petráková E. Yeh H.J.C. Ashwell G. Drgonová J. Kapteyn J.C. Klis F.M. Cabib E. J. Biol. Chem. 1997; 272: 17762-17775Abstract Full Text Full Text PDF PubMed Scopus (489) Google Scholar). In this complex, β(1→6)glucan occupies a central position. To it, chitin and β(1→3)glucan are directly attached by glycosidic linkages, whereas mannoprotein is joined to the polysaccharide through the lipidless remnant of a glycosylphosphatidylinositol anchor (Fig.1 B). These anchors have been identified as signals for the incorporation of proteins in the cell wall after transit through the plasma membrane (for review, see Ref. 7Lipke P.N. Ovalle R. J. Bacteriol. 1998; 180: 3735-3740Crossref PubMed Google Scholar). In a