Identifying a Novel Connection Between the Fungal Plasma Membrane and pH-Sensing.
Abstract
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. This article is protected by copyright. All rights reserved.
Type
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https://hdl.handle.net/10161/17195Published Version (Please cite this version)
10.1111/mmi.13998Publication Info
Brown, Hannah E; Ost, Kyla S; Esher, Shannon K; Pianalto, Kaila M; Saelens, Joseph
W; Guan, Ziqiang; & Andrew Alspaugh, J (2018). Identifying a Novel Connection Between the Fungal Plasma Membrane and pH-Sensing.
Molecular microbiology. 10.1111/mmi.13998. Retrieved from https://hdl.handle.net/10161/17195.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
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Show full item recordScholars@Duke
Ziqiang Guan
Research Professor in Biochemistry
We develop and apply mass spectrometry techniques to address biochemical and biomedical
questions that are lipid-related. Research projects include:
1) Structural lipidomics
o Develop and apply high resolution tandem mass spectrometry-based lipidomics for
the discovery, structural elucidation and functional study of novel lipids.
2) Elucidation of novel pathways/enzymes of lipid biosynthesis and metabolism
o Genetic, biochemical and MS a

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