Nutrient Sensing at the Plasma Membrane of Fungal Cells

Abstract

To respond to the changing environment, cells must be able to sense external conditions. This is important for many processes including growth, mating, the expression of virulence factors, and several other regulatory effects. Nutrient sensing at the plasma membrane is mediated by different classes of membrane proteins that activate downstream signaling pathways: nontransporting receptors, transceptors, classical and nonclassical G-protein-coupled receptors, and the newly defined extracellular mucin receptors. Nontransporting receptors have the same structure as transport proteins, but have lost the capacity to transport while gaining a receptor function. Transceptors are transporters that also function as a receptor, because they can rapidly activate downstream signaling pathways. In this review, we focus on these four types of fungal membrane proteins. We mainly discuss the sensing mechanisms relating to sugars, ammonium, and amino acids. Mechanisms for other nutrients, such as phosphate and sulfate, are discussed briefly. Because the model yeast Saccharomyces cerevisiae has been the most studied, especially regarding these nutrient-sensing systems, each subsection will commence with what is known in this species.

FIGURE 1

Sugar-sensing proteins in the plasma membrane of fungal cells. Nutrient-sensing proteins in general can be divided into nontransporting receptors, transceptors, and G-protein-coupled receptors (GPCRs). Nontransporting sugar receptors include the Saccharomyces cerevisiae (Sc) glucose sensors Snf3/Rgt2, the Kluyveromyces lactis (Kl) glucose sensor Rag4, the Hansenula polymorpha (Hp) glucose sensor Hxs1, the Candida albicans (Ca) glucose sensor Hgt4, the Cryptococcus neoformans (Cn) inositol sensor Itr1, the Trichoderma reesei (Tr) cellobiose sensor Crt1, and the Cn cellodextrin sensor Clp1. Sugar transceptors include the Ca glucose sensor Hgt12, the Cn hexose sensors Hxs1/2, the Hp hexose sensor Gcr1, the Neurospora crassa (Nc) sugar sensor Rco3, the Colletotrichum graminicola (Cg) hexose sensor Hxt4, the Ustilago maydis (Um) hexose sensor Hxt1, the Nc cellobiose sensors Cdt1/2, and the Trichoderma reesei (Tc) cellobiose sensor Stp1. Sugar GPCRs include the Sc glucose sensor Gpr1, the Cn glucose sensors Gpr4/5, the Nc glucose sensor Gpr4, the Aspergillus nidulans (An) glucose sensors GprD/H, the Aspergillus fumigatus (Af) glucose sensors GprC/D, and the Aspergillus flavus (Af) glucose sensors GprA/C/J/K/R.

FIGURE 2

Nitrogen-sensing proteins in the plasma membrane of fungal cells. Nutrient-sensing proteins, in general, can be divided into nontransporting receptors, transceptors, and G-protein-coupled receptors (GPCRs). Nontransporting nitrogen receptors include the Saccharomyces cerevisiae (Sc) amino acid sensor Ssy1, the Candida albicans (Ca) amino acid sensor Csy1, and an unknown Cryptococcus neoformans (Cn) amino acid sensor. Nitrogen transceptors include the Sc amino acid sensor Gap1, the Ca amino acid sensors Gap1/2/6, the Sc ammonium sensor Mep2, the Ca ammonium sensor Mep2, the Ustilago maydis (Um) ammonium sensor Ump2, the Fusarium fujikuroi (Ff) ammonium sensors MepA-C, the Hebeloma cylindrosporum (Hc) ammonium sensors Amt1-3, the Tuber borchii (Tb) ammonium sensor Amt1, and the Colletotrichum gloeosporioides (Cg) ammonium sensors MepA-C. Nitrogen GPCRs include the Ca methionine sensor Gpr1, the Cn amino acid sensor Gpr4, the Aspergillus nidulans (An) tryptophan sensor GprH, the Aspergillus flavus (Af) proline sensor GprC/D, the Schyzosaccharomyces pombe (Sp) nitrogen sensor Stm1, and the Af ammonium sensor GprR.

FIGURE 3

Surface-sensing proteins in the plasma membrane of fungal cells. Characterized surface-sensing proteins can be divided into G-protein-coupled receptors (GPCRs) and the interacting Sho receptors and the extracellular mucin receptors. The nonclassical, Pth11-type, GPCRs include the Magnaporthe oryzae (Mo) Pth11 receptor of hydrophobic surfaces and the Neurospora crassa (Nc) Gpr32, Gpr36, and Gpr39 putative lignocellulose receptors. The Sho receptors include the orthologous Ustilago maydis (Um), Fusarium oxysporum (Fo) and Mo, hydrophobic surface Sho1 receptors. The extracellular mucins include the orthologous Aspergillus nidulans (An), Um, Fo, Mo, Msb2 hydrophobic surface receptors, in addition to the Msb2 receptors of Candida albicans (Ca) and Saccharomyces cerevisiae (Sc) that have not been characterized as detecting surfaces, plus the additional Cbp1 mucin receptor of hydrophobic surfaces from Mo.

FIGURE 4

Nutrient- and surface-sensing proteins in the plasma membrane of fungal cells and the downstream signal transduction pathways they trigger. Examples for the different classes of nutrient (nontransporting receptors, transceptors, and GPCRs) and surface (mucin and Sho) sensing proteins are shown. Sensing of nutrients by nontransporting receptors and sugar transceptors results in the induction of nutrient transporter genes. Nitrogen transceptors (e.g., ScGap1) result in the activation of the PKA pathway upon sensing appropriate nitrogen sources. Depending on the type of GPCR, they can activate the cAMP-PKA pathway, the MAPK pathway, or both. The surface receptors activate the MAPK pathway.