The cAMP/protein kinase A signaling pathway in pathogenic basidiomycete fungi: Connections with iron homeostasis

Abstract

A number of pathogenic species of basidiomycete fungi are either life-threatening pathogens of humans or major economic pests for crop production. Sensing the host is a key aspect of pathogen proliferation during disease, and signal transduction pathways are critically important for detecting environmental conditions and facilitating adaptation. This review focuses on the contributions of the cAMP/protein kinase A (PKA) signaling pathway in Cryptococcus neoformans, a species that causes meningitis in humans, and Ustilago maydis, a model phytopathogen that causes a smut disease on maize. Environmental sensing by the cAMP/PKA pathway regulates the production of key virulence traits in C. neoformans including the polysaccharide capsule and melanin. For U. maydis, the pathway controls the dimorphic transition from budding growth to the filamentous cell type required for proliferation in plant tissue. We discuss recent advances in identifying new components of the cAMP/PKA pathway in these pathogens and highlight an emerging theme that pathway signaling influences iron acquisition.

Fig. 1. The pheromone response MAPK and cAMP signaling pathways in C. neoformans and U. maydis

The known input signals are indicated at the top of each pathway (at the level of the plasma membrane) and the key identified components of the pathways are shown below as ovals. The position of Rak1 in U. maydis is shown as influencing ribosomes and the transcription factor Rop1 (Wang et al., 2011). A speculative position for Rak1 at the level of G protein signaling is also shown for U. maydis and indicated with a question mark based on the findings in C. neoformans (Wang et al., 2014). In addition, Rim101 and Urbs1 are positioned as potential downstream targets of the protein kinase A catalytic subunit Adr1. Solid arrows indicate the flow of signals through the pathways with dotted arrows representing the influence on downstream target phenotypes. The representations of the signaling pathways are based on previous reviews and the recent findings (Regenfelder et al., 1997; Muller et al., 2004; Arechiga-Carvajal and Ruiz-Herrera, 2005; Klosterman et al., 2007; Kozubowski et al., 2009; Wang et al., 2011, 2014; Kronstad et al., 2011a; Kozubowski and Heitman, 2012; Donlin et al., 2014; Roach et al., 2014). Details on additional signaling components can be found in these reviews.