Identifying a Novel Connection Between the Fungal Plasma Membrane and pH-Sensing.

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2018-06-08

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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.

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10.1111/mmi.13998

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Brown, Hannah E, Kyla S Ost, Shannon K Esher, Kaila M Pianalto, Joseph W Saelens, Ziqiang Guan and J Andrew Alspaugh (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.

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Scholars@Duke

Guan

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 approaches are employed to identify the substrates and pathways involved in lipid biosynthesis and metabolism

3) Identification of lipid biomarkers of genetic diseases and cancers

o    Provide molecular insights into the disease mechanisms, as well as to serve as the diagnostic and prognostic tools of diseases.


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