Conservation in Aspergillus fumigatus of pH-signaling seven transmembrane domain and arrestin proteins, and implications for drug discovery

    Research output: Contribution to journalArticlepeer-review

    Abstract

    Adaptation to extracellular pH is a major challenge to fungal pathogens that infect mammalian hosts. Among pH responses mounted by diverse fungal pathogens there is a high degree of molecular conservation. This, coupled with the absence of such signaling pathways in mammalian cells, suggests that this crucial fungal survival mechanism might provide a useful means of limiting a broad spectrum of infectious fungal growth. PacC/Rim signaling converts extracellular cues, perceived by the fungal cell at extremes of ambient pH, into a cellular signal moderating the activation and/or derepression of multiple pH-sensitive gene functions including enzymes, permeases, and transporters. Signal transduction via the fungal PacC/Rim pathway involves a seven transmembrane domain (7TMD) receptor-arrestin protein complex. This review will discuss, with particular attention to Aspergillus fumigatus (the major mold pathogen of humans), the conservation of PacC/Rim signal reception proteins, and protein domains, required for tolerance of pH change, and pathogenicity, and the significance of such molecules as targets for interventive therapies. © 2012 New York Academy of Sciences.
    Original languageEnglish
    Pages (from-to)35-43
    Number of pages8
    JournalAnnals of the New York Academy of Sciences
    Volume1273
    Issue number1
    DOIs
    Publication statusPublished - Dec 2012

    Keywords

    • Arrestin
    • Aspergillus
    • PH receptor
    • Plasma membrane
    • Signal transduction

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