Ambient pH gene regulation in fungi: making connections

Abstract

Many fungi grow over a wide pH range and their gene expression is tailored to the environmental pH. In Aspergillus nidulans, the transcription factor PacC, an activator of genes expressed in alkaline conditions and a repressor of those expressed in acidic conditions, undergoes two processing proteolyses, the first being pH-signal dependent and the second proteasomal. Signal transduction involves a 'go-between' connecting two complexes, one of which comprises two plasma membrane proteins and an arrestin and the other comprises PacC, a cysteine protease, a scaffold and endosomal components. The Saccharomyces cerevisiae PacC orthologue, Rim101p, differs in that it does not undergo the second round of proteolysis and it functions directly as a repressor only. PacC/Rim101-mediated pH regulation is crucial to fungal pathogenicity.

Functional Genomics Analysis of theSaccharomyces cerevisiaeIron Responsive Transcription Factor Aft1 Reveals Iron-Independent Functions

“…The fact that many of the mutants identified in the AFT1 network are not sensitive to extracellular free iron concentrations or genetically interact with aft2D or fet3D suggests that Aft1 may affect numerous processes independently of iron homeostasis. Aft1 and the RIM101 pH response pathway function in parallel: A striking feature of the AFT1 genetic network is the identification of numerous genes with established roles in the RIM101 pH response pathway (reviewed in Penalva et al 2008). The RIM101 pH pathway plays a role in the transcriptional response to alkaline pH (Lamb et al 2001), as well as cell-wall assembly (Castrejon et al 2006), sporulation (Su and Mitchell 1993;Li and Mitchell 1997), and ion homeostasis (Lamb et al 2001).…”

“…The cleavage of Rim101 is tightly regulated by a variety of processing gene products including the putative transmembrane proteins Rim21 and Rim9, the arrestin-like protein Rim8, the protease Rim13, and the protease scaffold protein Rim20 (reviewed in Penalva et al 2008). The pH signal transduction and activation of Rim101 also requires ESCRT (endosomal sorting complex required for transport) complexes I, II, and the Snf7-Vps20 subcomplex of ESCRT-III (reviewed in Penalva et al 2008). In addition to RIM101, the AFT1 genetic network identified RIM9, Figure 1.-Genetic interaction network of AFT1, AFT2, FET3, and RIM101.…”

“…In contrast, the expression of ARN1 (Lamb and Mitchell 2003;Barwell et al 2005), FRE1 (Lamb et al 2001), and a FET3-lacZ reporter (Figure 2) is increased in the absence of Rim101 in alkaline treatment. Rim101 functions as a repressor through binding of promoters (reviewed in Penalva et al 2008) and indirectly as an activator through the repression of negative-acting genes SMP1 and NRG1 (Lamb and Mitchell 2003). Could Rim101 be acting as both a repressor and activator of a subset of iron regulon genes?…”

Virulence Regulation of Phytopathogenic Fungi by pH

“…In its active form PACC 27 is translocated to the nucleus, where the zinc-finger region recognizes the consensus DNA site 5¢-GCCARG (96,147). PACC regulation has been most extensively studied in the genus Aspergillus, but it was also found in many other fungi (6,117). However, few publications have described the whole amount of genes that might be regulated by PACC specifically during fungal pathogenicity (53, 159).…”

“…PAL regulation mechanism of PACC transcription factor at alkaline surroundings. The figure is adapted from (60,117). In alkaline pH conditions activated PalH transmits a signal across the membrane resulting in the activation PalF, which becomes ubiquitylated.…”