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Identifying a novel connection between the fungal plasma membrane and pH‐sensing
Author(s) -
Brown Hannah E.,
Ost Kyla S.,
Esher Shan K.,
Pianalto Kaila M.,
Saelens Joseph W.,
Guan Ziqiang,
Andrew Alspaugh J.
Publication year - 2018
Publication title -
molecular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 247
eISSN - 1365-2958
pISSN - 0950-382X
DOI - 10.1111/mmi.13998
Subject(s) - biology , cryptococcus neoformans , insertional mutagenesis , signal transduction , microbiology and biotechnology , mutant , biochemistry , extracellular , fungal protein , gene
Summary The mechanisms by which micro‐organisms sense and internalize extracellular pH signals are not completely understood. One example of a known external pH‐sensing process is the fungal‐specific Rim/Pal signal transduction pathway. Fungi, such as the opportunistic pathogen Cryptococcus neoformans , use Rim signaling to sense and respond to changes in environmental pH. Mutations in this pathway result in strains that are attenuated for survival at alkaline pH, and often for survival within the host. Here, we used an insertional mutagenesis screen to identify novel genes required for C. neoformans growth at host pH. We discovered altered alkaline pH growth in several strains with specific defects in plasma membrane composition and maintenance of phospholipid assembly. Among these, loss of function of the Cdc50 lipid flippase regulatory subunit affected the temporal dynamics of Rim pathway activation. We defined distinct and overlapping cellular processes regulated by Rim101 and Cdc50 through analysis of the transcriptome in these mutant strains. We further explored how pH‐induced membrane changes affect membrane‐bound pH‐sensing proteins, specifically the C‐terminal domain of the Rra1 protein, an upstream Rim pathway activator and pH sensor. These results suggest both broadly applicable and phylum‐specific molecular interactions that drive microbial environmental sensing.