The Cryptococcus neoformans Flc1 Homologue Controls Calcium Homeostasis and Confers Fungal Pathogenicity in the Infected Hosts

Stempinski, Piotr R; Goughenour, Kristie D.; Plooy, Lukas M. du; Alspaugh, J. Andrew; Olszewski, Michal A.; Kozubowski, Lukasz

doi:10.1128/mbio.02253-22

Cited by 8 publications

(10 citation statements)

References 90 publications

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“…Calcineurin is a Ca 2+ -calmodulin-dependent phosphatase, which in C. neoformans is activated predominantly by heat stress, but also by exogenous Ca 2+ and cell wall stress ( 30 ). This leads to dephosphorylation of the transcription factor Crz1 and its translocation to the nucleus ( 30 , 44 ) to induce the expression of genes involved in cell wall integrity and response to oxidative stress ( 30 – 32 ). To further explore the connection between the PHO and calcineurin pathways, we investigated whether altering cellular P i affects the calcineurin activation response.…”

Section: Resultsmentioning

confidence: 99%

Dysregulating PHO Signaling via the CDK Machinery Differentially Impacts Energy Metabolism, Calcineurin Signaling, and Virulence in Cryptococcus neoformans

Bowring

Sethiya

Desmarini

et al. 2023

mBio

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Section: Resultsmentioning

confidence: 99%

Dysregulating PHO Signaling via the CDK Machinery Differentially Impacts Energy Metabolism, Calcineurin Signaling, and Virulence in Cryptococcus neoformans

Bowring

Sethiya

Desmarini

et al. 2023

mBio

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“…Recently, transient receptor potential (TRP) channels were found among mammals, flies, worms, ciliates, Chlamydomonas and yeasts [ 45 ]. The TRP channels act as sensors for various stresses, including temperature, pH, osmolarity and nutrient availability [ 46 , 47 , 48 , 49 ]. The first calcium-permeable TRP, initially isolated from Arabidopsis thaliana , can be activated by hyperosmotic shock and, therefore, was named calcium-permeable stress-gated cation channel 1 (CSC1) [ 47 ], which includes the PenV protein of P. chrysogenum and CefP of A. chrysogenum [ 50 ].…”

Section: Calcium Signaling Pathway In Fungal Cellmentioning

confidence: 99%

“…The Yvc1 channel protein located on the tonoplast is a homologue of mammalian transient receptor potential (TRP) channel protein responsible for the release of Ca 2+ from the vacuole into the cytoplasm [ 10 , 51 , 52 ]. FLC was recently proposed as a member of the FLC family required for importing FAD into the endoplasmic reticulum, and it represent a conserved fungal gene family of integral membrane protein, spanning a TRP-like domain [ 49 , 53 ]. Some studies suggest FLC could act as either a calcium sensor or directly as a calcium channel [ 49 ].…”

Section: Calcium Signaling Pathway In Fungal Cellmentioning

confidence: 99%

“…FLC was recently proposed as a member of the FLC family required for importing FAD into the endoplasmic reticulum, and it represent a conserved fungal gene family of integral membrane protein, spanning a TRP-like domain [ 49 , 53 ]. Some studies suggest FLC could act as either a calcium sensor or directly as a calcium channel [ 49 ].…”

Section: Calcium Signaling Pathway In Fungal Cellmentioning

confidence: 99%

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Updating Insights into the Regulatory Mechanisms of Calcineurin-Activated Transcription Factor Crz1 in Pathogenic Fungi

Yang

Xie

et al. 2022

JoF

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Ca2+, as a second messenger in cells, enables organisms to adapt to different environmental stresses by rapidly sensing and responding to external stimuli. In recent years, the Ca2+ mediated calcium signaling pathway has been studied systematically in various mammals and fungi, indicating that the pathway is conserved among organisms. The pathway consists mainly of complex Ca2+ channel proteins, calcium pumps, Ca2+ transporters and many related proteins. Crz1, a transcription factor downstream of the calcium signaling pathway, participates in regulating cell survival, ion homeostasis, infection structure development, cell wall integrity and virulence. This review briefly summarizes the Ca2+ mediated calcium signaling pathway and regulatory roles in plant pathogenic fungi. Based on discussing the structure and localization of transcription factor Crz1, we focus on the regulatory role of Crz1 on growth and development, stress response, pathogenicity of pathogenic fungi and its regulatory mechanisms. Furthermore, we explore the cross-talk between Crz1 and other signaling pathways. Combined with the important role and pathogenic mechanism of Crz1 in fungi, the new strategies in which Crz1 may be used as a target to explore disease control in practice are also discussed.

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“…It has been found that these proteins not only possess Ca 2+ regulatory functions but also assume distinctive and significant roles in their respective species ( 22 – 25 ). In the opportunistic yeast pathogen Cryptococcus neoformans , Flc1, a homolog of FLC family proteins found in the genome of S. cerevisiae , has been postulated to be essential for regulating stress response and virulence ( 26 , 27 ). Additionally, the deficiency of Flc1 in C. neoformans leads to an abnormal distribution of chitin, the inhibition of vacuole fusion, and the disruption of autophagy ( 26 , 27 ).…”

Section: Introductionmentioning

confidence: 99%

The versatility of the putative transient receptor potential ion channels in regulating the calcium signaling in Aspergillus nidulans

Wang,

Gao,

Zhang

et al. 2023

mSphere

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Transient receptor potential (TRP) channels are evolutionarily conserved integral membrane proteins. They serve as crucial mediators of sensory signals and have profound effects on cellular functions. However, many functions of the TRP family remain to be explored. In this study, the biological functions of three potential TRP channels, TrpA, TrpB, and TrpC, in Aspergillus nidulans have been verified. Green fluorescent protein labeling indicated that these TRP channels have distinct localization patterns. TrpA was primarily located at hyphal tips, TrpB showed a localization pattern resembling the Golgi apparatus, and TrpC displayed a possible ER-like localization pattern. Findings suggested that these TRP channels may be involved in different physiological processes. Deletion or reduced expression of TrpA resulted in severe growth defects and abolished conidiation. Moreover, TrpA may have multiple roles during fungal development, as TrpA mutants caused significant changes in gene expression. The lack of TrpB resulted in colony defects in a calcium-dependent manner, especially under high-temperature conditions. These defects in Δ trpB can be largely rescued by adding calcium, indicating that TrpB is required in low-calcium conditions. The deletion of TrpC did not exhibit any detectable phenotypes under tested cultural conditions. However, when major calcium channels MidA/CchA or PmrA were absent, the lack of TrpC further exacerbated the colony defects, implying that TrpC serves as a supplementary function. In conclusion, TRP channels are involved in a wide range of physiological processes and findings provide a valuable reference for investigating the functions of TRP proteins in other fungal or eukaryotic species. IMPORTANCE Transient receptor potential (TRP) ion channels are evolutionarily conserved integral membrane proteins with non-selective ion permeability, and they are widely distributed in mammals and single-cell yeast and serve as crucial mediators of sensory signals. However, the relevant information concerning TRP channels in Aspergillus nidulans remains inadequately understood. In this study, by gene deletion, green fluorescent protein tagging, and cytosolic Ca 2+ transient monitoring techniques, the biological functions of three potential TRP channels (TrpA, TrpB, and TrpC) have been explored for which they play distinct and multiple roles in hyphal growth, conidiation, responsiveness to external stress, and regulation of intracellular Ca 2+ homeostasis. The findings of this study on the functions of potential TRP channels in A. nidulans may serve as a valuable reference for understanding the roles of TRP homologs in industrial or medical strains of Aspergillus , as well as in other filamentous fungi.

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The Cryptococcus neoformans Flc1 Homologue Controls Calcium Homeostasis and Confers Fungal Pathogenicity in the Infected Hosts

Abstract: Cryptococcosis is a highly lethal infection with limited drug choices, most of which are highly toxic or complicated by emerging antifungal resistance. There is a great need for new drug targets that are unique to the fungus.

Cited by 8 publications

References 90 publications

Dysregulating PHO Signaling via the CDK Machinery Differentially Impacts Energy Metabolism, Calcineurin Signaling, and Virulence in Cryptococcus neoformans

Dysregulating PHO Signaling via the CDK Machinery Differentially Impacts Energy Metabolism, Calcineurin Signaling, and Virulence in Cryptococcus neoformans

Updating Insights into the Regulatory Mechanisms of Calcineurin-Activated Transcription Factor Crz1 in Pathogenic Fungi

The versatility of the putative transient receptor potential ion channels in regulating the calcium signaling in Aspergillus nidulans

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