Characterization of additional components of the environmental pH-sensing complex in the pathogenic fungus Cryptococcus neoformans.
Abstract
Pathogenic microorganisms must adapt to changes in their immediate surroundings, including
alterations in pH, to survive the shift from the external environment to that of the
infected host. In the basidiomycete fungal pathogen Cryptococcus neoformans, these
pH changes are primarily sensed by the fungus-specific, alkaline pH-sensing Rim/Pal
pathway. The C. neoformans Rim pathway has diverged significantly from that described
in ascomycete fungi. We recently identified the C. neoformans putative pH sensor Rra1,
which activates the Rim pathway in response to elevated pH. In this study, we probed
the function of Rra1 by analyzing its cellular localization and performing protein
co-immunoprecipitation to identify potential Rra1 interactors. We found that Rra1
does not strongly colocalize or interact with immediate downstream Rim pathway components.
However, these experiments identified a novel Rra1 interactor, the previously uncharacterized
C. neoformans nucleosome assembly protein 1 (Nap1), which was required for Rim pathway
activation. We observed that Nap1 specifically binds to the C-terminal tail of the
Rra1 sensor, probably promoting Rra1 protein stability. This function of Nap1 is conserved
in fungi closely related to C. neoformans that contain Rra1 orthologs, but not in
the more distantly related ascomycete fungus Saccharomyces cerevisiae In conclusion,
our findings have revealed the sophisticated, yet distinct, molecular mechanisms by
which closely and distantly related microbial phyla rapidly adapt to environmental
signals and changes, such as alterations in pH.
Type
Journal articleSubject
Nap1Rim pathway
cell signaling
environmental sensing
fungi
microbial pathogenesis
molecular biology
pH sensing
protein stability
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https://hdl.handle.net/10161/17691Published Version (Please cite this version)
10.1074/jbc.ra118.002741Publication Info
Pianalto, Kaila M; Ost, Kyla S; Brown, Hannah E; & Alspaugh, J Andrew (2018). Characterization of additional components of the environmental pH-sensing complex
in the pathogenic fungus Cryptococcus neoformans. The Journal of biological chemistry, 293(26). pp. 9995-10008. 10.1074/jbc.ra118.002741. Retrieved from https://hdl.handle.net/10161/17691.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
James Andrew Alspaugh II
Professor of Medicine
The focus of my research is to understand the ways in which microorganisms sense and
respond to changes in their environment. As microbial pathogens enter the infected
host, dramatic genetic and phenotypic events occur that allow these organisms to survive
in this harsh environment. We study the model fungal organism Cryptococcus neoformans
to define signal transduction pathways associated with systemic fungal diseases. This
pathogenic fungus causes lethal infections of the central nervou

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