Molecular Dissection of Crz1 and Its Dynamic Subcellular Localization in <i>Cryptococcus neoformans</i>

Across lower eukaryotes, the transcription factor Crz1 is dephosphorylated by calcineurin, which facilitates Crz1 translocation to the nucleus to regulate gene expression. In the fungal pathogen <i>Cryptococcus neoformans</i>, calcineurin–Crz1 signaling maintains calcium homeostasis, the...

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Main Authors: Benjamin J. Chadwick, Brittain Elizabeth Ross, Xiaorong Lin
Format: Article
Language:English
Published: MDPI AG 2023-02-01
Series:Journal of Fungi
Subjects:
Online Access:https://www.mdpi.com/2309-608X/9/2/252
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author Benjamin J. Chadwick
Brittain Elizabeth Ross
Xiaorong Lin
author_facet Benjamin J. Chadwick
Brittain Elizabeth Ross
Xiaorong Lin
author_sort Benjamin J. Chadwick
collection DOAJ
description Across lower eukaryotes, the transcription factor Crz1 is dephosphorylated by calcineurin, which facilitates Crz1 translocation to the nucleus to regulate gene expression. In the fungal pathogen <i>Cryptococcus neoformans</i>, calcineurin–Crz1 signaling maintains calcium homeostasis, thermotolerance, cell wall integrity, and morphogenesis. How Crz1 distinguishes different stressors and differentially regulates cellular responses is poorly understood. Through monitoring Crz1 subcellular localization over time, we found that Crz1 transiently localizes to granules after exposure to high temperature or calcium. These granules also host the phosphatase calcineurin and Pub1, a ribonucleoprotein stress granule marker, suggesting a role of stress granules in modulating calcineurin–Crz1 signaling. Additionally, we constructed and analyzed an array of Crz1 truncation mutants. We identified the intrinsically disordered regions in Crz1 contribute to proper stress granule localization, nuclear localization, and function. Our results provide the groundwork for further determination of the mechanisms behind the complex regulation of Crz1.
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spelling doaj.art-25b2956596474c4fb65af71e78334f5d2023-11-16T21:31:10ZengMDPI AGJournal of Fungi2309-608X2023-02-019225210.3390/jof9020252Molecular Dissection of Crz1 and Its Dynamic Subcellular Localization in <i>Cryptococcus neoformans</i>Benjamin J. Chadwick0Brittain Elizabeth Ross1Xiaorong Lin2Department of Plant Biology, University of Georgia, Athens, GA 30602, USADepartment of Plant Biology, University of Georgia, Athens, GA 30602, USADepartment of Plant Biology, University of Georgia, Athens, GA 30602, USAAcross lower eukaryotes, the transcription factor Crz1 is dephosphorylated by calcineurin, which facilitates Crz1 translocation to the nucleus to regulate gene expression. In the fungal pathogen <i>Cryptococcus neoformans</i>, calcineurin–Crz1 signaling maintains calcium homeostasis, thermotolerance, cell wall integrity, and morphogenesis. How Crz1 distinguishes different stressors and differentially regulates cellular responses is poorly understood. Through monitoring Crz1 subcellular localization over time, we found that Crz1 transiently localizes to granules after exposure to high temperature or calcium. These granules also host the phosphatase calcineurin and Pub1, a ribonucleoprotein stress granule marker, suggesting a role of stress granules in modulating calcineurin–Crz1 signaling. Additionally, we constructed and analyzed an array of Crz1 truncation mutants. We identified the intrinsically disordered regions in Crz1 contribute to proper stress granule localization, nuclear localization, and function. Our results provide the groundwork for further determination of the mechanisms behind the complex regulation of Crz1.https://www.mdpi.com/2309-608X/9/2/252<i>Cryptococcus neoformans</i>calcineurinCrz1stress granulesintrinsically disordered regions
spellingShingle Benjamin J. Chadwick
Brittain Elizabeth Ross
Xiaorong Lin
Molecular Dissection of Crz1 and Its Dynamic Subcellular Localization in <i>Cryptococcus neoformans</i>
Journal of Fungi
<i>Cryptococcus neoformans</i>
calcineurin
Crz1
stress granules
intrinsically disordered regions
title Molecular Dissection of Crz1 and Its Dynamic Subcellular Localization in <i>Cryptococcus neoformans</i>
title_full Molecular Dissection of Crz1 and Its Dynamic Subcellular Localization in <i>Cryptococcus neoformans</i>
title_fullStr Molecular Dissection of Crz1 and Its Dynamic Subcellular Localization in <i>Cryptococcus neoformans</i>
title_full_unstemmed Molecular Dissection of Crz1 and Its Dynamic Subcellular Localization in <i>Cryptococcus neoformans</i>
title_short Molecular Dissection of Crz1 and Its Dynamic Subcellular Localization in <i>Cryptococcus neoformans</i>
title_sort molecular dissection of crz1 and its dynamic subcellular localization in i cryptococcus neoformans i
topic <i>Cryptococcus neoformans</i>
calcineurin
Crz1
stress granules
intrinsically disordered regions
url https://www.mdpi.com/2309-608X/9/2/252
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AT xiaoronglin moleculardissectionofcrz1anditsdynamicsubcellularlocalizationinicryptococcusneoformansi