Generating anchors only to lose them: The unusual story of glycosylphosphatidylinositol anchor biosynthesis and remodeling in yeast and fungi

Abstract

Glycosylphosphatidylinositol (GPI)-anchored proteins (GPI-APs) are present ubiquitously at the cell surface in all eukaryotes. They play a crucial role in the interaction of the cell with its external environment, allowing the cell to receive signals, respond to challenges, and mediate adhesion. In yeast and fungi, they also participate in the structural integrity of the cell wall and are often essential for survival. Roughly four decades after the discovery of the first GPI-APs, this review provides an overview of the insights gained from studies of the GPI biosynthetic pathway and the future challenges in the field. In particular, we focus on the biosynthetic pathway in Saccharomyces cerevisiae, which has for long been studied as a model organism. Where available, we also provide information about the GPI biosynthetic steps in other yeast/ fungi. Although the core structure of the GPI anchor is conserved across organisms, several variations are built into the biosynthetic pathway. The present Review specifically highlights these variations and their implications. There is growing evidence to suggest that several phenotypes are common to GPI deficiency and should be expected in GPI biosynthetic mutants. However, it appears that several phenotypes are unique to a specific step in the pathway and may even be species-specific. These could suggest the points at which the GPI biosynthetic pathway intersects with other important cellular pathways and could be points of regulation. They could be of particular significance in the study of pathogenic fungi and in identification of new and specific antifungal drugs/ drug targets. © 2018 IUBMB Life, 70(5):355-383, 2018.

Function ofAtPGAP1in GPI anchor lipid remodeling and transport to the cell surface of GPI-anchored proteins

“…In humans, null mutations of PGAP1 are viable but result in defects in neuronal cell function (Ueda et al, 2007; Murakami et al, 2014; Williams et al, 2015). ScBst1 is non-essential in yeast (Komath et al, 2018) and ScBst1 mutants grew as well as wild-type at all temperatures (Elrod-Erickson and Kaiser, 1996; Fujita et al, 2006b). In Candida Albicans , deletion of Bst1 impaired host infection and caused altered cell wall polysaccharides (Liu et al, 2016).…”

Diversity of GPI-anchored fungal adhesins

“…So far, only a few fungal genes belonging to the Dfg5/Dcw1 family have been identified, which are involved in adhesion and cell wall anchoring and that have been suggested to act as enzymes catalysing the membrane-to-wall transfer of GPI-CWP adhesins (Ao et al 2015;Maddi et al 2012;Mösch and Fink 1997;Muszkieta et al 2019;Spreghini et al 2003). Accordingly, we discuss the mechanisms of GPI-adhesin maturation and incorporation into the cell wall given our current understanding of fungal GPI biosynthesis and remodelling (Kinoshita and Fujita 2016;Komath et al 2018).…”

The subcellular organisation of Saccharomyces cerevisiae

“…Different isoforms of the leucine aminopeptidase Lap3 exhibit different subcellular localisations, with the canonical isoform being located at the mitochondrion and a truncated isoform localised elsewhere [11 •• ]. Localisation is significantly influenced by post-translational modifications such as phosphorylation, which affects the localisation of transcription factors to the nucleus in multiple biological systems [12, 13, 14], and addition of glycophosphatidylinositol anchors that anchors proteins to cellular membrane [15]. Finally, a protein’s final location may be dictated by the site of its translation as some transcripts are localised to an organelle before translation, sometimes by specific protein families such as the RNA-binding PUF protein family, members of which can transport transcripts to the ER [16] and mitochondria [17].…”