Cryptococcal Titan Cell Formation Is Regulated by G-Protein Signaling in Response to Multiple Stimuli

ABSTRACT The titan cell is a recently described morphological form of the pathogenic fungus Cryptococcus neoformans . Occurring during the earliest stages of lung infection, titan cells are 5 to 10 times larger than the normal yeast-like cells, thereby resisting engulfment by lung phagocytes and favoring the persistence of infection. These enlarged cells exhibit an altered capsule structure, a thickened cell wall, increased ploidy, and resistance to nitrosative and oxidative stresses. We demonstrate that two G-protein-coupled receptors are important for induction of the titan cell phenotype: the Ste3 a pheromone receptor (in mating type a cells) and the Gpr5 protein. Both receptors control titan cell formation through elements of the cyclic AMP (cAMP)/protein kinase A (PKA) pathway. This conserved signaling pathway, in turn, mediates its effect on titan cells through the PKA-regulated Rim101 transcription factor. Additional downstream effectors required for titan cell formation include the G 1 cyclin Pcl103, the Rho104 GTPase, and two GTPase-activating proteins, Gap1 and Cnc1560. These observations support developing models in which the PKA signaling pathway coordinately regulates many virulence-associated phenotypes in diverse human pathogens.

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Heterotrimeric G-Protein Signalers and RGSs in Aspergillus fumigatus

Pathogens ◽

10.3390/pathogens9110902 ◽

2020 ◽

Vol 9 (11) ◽

pp. 902

Author(s):

Hee-Soo Park ◽

Min-Ju Kim ◽

Jae-Hyuk Yu ◽

Kwang-Soo Shin

Keyword(s):

Aspergillus Fumigatus ◽

Signaling Pathways ◽

Signaling Pathway ◽

G Protein ◽

G Proteins ◽

Pathogenic Fungus ◽

G Protein Signaling ◽

Protein Signaling ◽

Heterotrimeric G Protein ◽

External Signals

The heterotrimeric G-protein (G-protein) signaling pathway is one of the most important signaling pathways that transmit external signals into the inside of the cell, triggering appropriate biological responses. The external signals are sensed by various G-protein-coupled receptors (GPCRs) and transmitted into G-proteins consisting of the α, β, and γ subunits. Regulators of G-protein signaling (RGSs) are the key controllers of G-protein signaling pathways. GPCRs, G-proteins, and RGSs are the primary upstream components of the G-protein signaling pathway, and they are highly conserved in most filamentous fungi, playing diverse roles in biological processes. Recent studies characterized the G-protein signaling components in the opportunistic pathogenic fungus Aspergillus fumigatus. In this review, we have summarized the characteristics and functions of GPCRs, G-proteins, and RGSs, and their regulatory roles in governing fungal growth, asexual development, germination, stress tolerance, and virulence in A. fumigatus.

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IL-17 Activates the Canonical NF-κB Signaling Pathway in Autoimmune B Cells of BXD2 Mice To Upregulate the Expression of Regulators of G-Protein Signaling 16

The Journal of Immunology ◽

10.4049/jimmunol.0903133 ◽

2010 ◽

Vol 184 (5) ◽

pp. 2289-2296 ◽

Cited By ~ 60

Author(s):

Shutao Xie ◽

Jun Li ◽

John H. Wang ◽

Qi Wu ◽

PingAr Yang ◽

...

Keyword(s):

B Cells ◽

Signaling Pathway ◽

G Protein ◽

G Protein Signaling ◽

Protein Signaling

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Amplification systems of weak interaction biosensors: applications and prospects

Sensor Review ◽

10.1108/sr-03-2014-629 ◽

2015 ◽

Vol 35 (1) ◽

pp. 30-42 ◽

Cited By ~ 6

Author(s):

Xingya Wang ◽

Guangchang Pang

Keyword(s):

G Protein ◽

Weak Interaction ◽

Signal Amplification ◽

Signaling Cascade ◽

G Protein Signaling ◽

Protein Signaling ◽

Content Type ◽

Amplification Method ◽

Amplification System ◽

Cascade Amplification

Purpose – This paper aims to provide a detailed review of weak interaction biosensors and several common biosensor methods for magnifying signals, as well as judiciously guide readers through selecting an appropriate detecting system and signal amplification method according to their research and application purpose. Design/methodology/approach – This paper classifies the weak interactions between biomolecules, summarizes the common signal amplification methods used in biosensor design and compares the performance of different kinds of biosensors. It highlights a potential electrochemical signal amplification method: the G protein signaling cascade amplification system. Findings – Developed biosensors which, based on various principles, have their own strengths and weaknesses have met the basic detection requirements for weak interaction between biomolecules: the selectivity, sensitivity and detection limit of biosensors have been consistently improving with the use of new signal amplification methods. However, most of the weak interaction biosensors stop at the research stage; there are only a minority realization of final commercial application. Originality/value – This paper evaluates the status of research and application of weak interaction biosensors systematically. The G protein signaling cascade amplification system proposal offers a new avenue for the research and development of electrochemical biosensors.

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Single Nucleotide Polymorphisms in G Protein Signaling Pathway Genes in Preeclampsia

Hypertension ◽

10.1161/hypertensionaha.111.00331 ◽

2013 ◽

Vol 61 (3) ◽

pp. 655-661 ◽

Cited By ~ 31

Author(s):

Anne Stine Kvehaugen ◽

Øyvind Melien ◽

Oddgeir Lingaas Holmen ◽

Hannele Laivuori ◽

Pål Øian ◽

...

Keyword(s):

Single Nucleotide Polymorphisms ◽

Signaling Pathway ◽

G Protein ◽

G Protein Signaling ◽

Nucleotide Polymorphisms ◽

Protein Signaling ◽

Single Nucleotide

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Nuclear translocation of nuclear factor kappa B is regulated by G protein signaling pathway in arsenite-induced apoptosis in HBE cell line

Environmental Toxicology ◽

10.1002/tox.22183 ◽

2015 ◽

Vol 31 (12) ◽

pp. 1819-1833 ◽

Cited By ~ 8

Author(s):

Chengzhi Chen ◽

Shiyan Gu ◽

Xuejun Jiang ◽

Zunzhen Zhang

Keyword(s):

Cell Line ◽

Signaling Pathway ◽

G Protein ◽

Nuclear Factor Kappa B ◽

Nuclear Translocation ◽

G Protein Signaling ◽

Nuclear Factor ◽

Protein Signaling ◽

Nuclear Factor Kappa ◽

Induced Apoptosis

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Evidence for a Role of the Regulator of G-Protein Signaling Protein CPRGS-1 in Gα Subunit CPG-1-Mediated Regulation of Fungal Virulence, Conidiation, and Hydrophobin Synthesis in the Chestnut Blight Fungus Cryphonectria parasitica

Eukaryotic Cell ◽

10.1128/ec.3.6.1454-1463.2004 ◽

2004 ◽

Vol 3 (6) ◽

pp. 1454-1463 ◽

Cited By ~ 36

Author(s):

Gerrit C. Segers ◽

Jerome C. Regier ◽

Donald. L. Nuss

Keyword(s):

G Protein ◽

Pathogenic Fungus ◽

Aerial Mycelium ◽

Cryphonectria Parasitica ◽

Chestnut Blight ◽

G Protein Signaling ◽

Protein Signaling ◽

Fungal Virulence ◽

Chestnut Blight Fungus ◽

Rgs Protein

ABSTRACT We previously reported that the chestnut blight fungus Cryphonectria parasitica expresses at least three G-protein α subunits and that Gα subunit CPG-1 is essential for regulated growth, pigmentation, sporulation, and virulence. We now report the cloning and characterization of a C. parasitica regulator of G-protein signaling (RGS) protein, CPRGS-1. The phylogenetic relationship of CPRGS-1 to orthologs from other fungi was inferred and found to be generally concordant with species relationships based on 18S ribosomal sequences and on morphology. However, Hemiascomycotine RGS branch lengths in particular were longer than for their 18S sequence counterparts, which correlates with functional diversification in the signaling pathway. Deletion of cprgs-1 resulted in reduced growth, sparse aerial mycelium, and loss of pigmentation, sporulation, and virulence. Disruption of cprgs-1 was also accompanied by a severe posttranscriptional reduction in accumulation of CPG-1 and Gβ subunit CPGB-1 and severely reduced expression of the hydrophobin-encoding gene cryparin. The changes in phenotype, cryparin expression, and CPGB-1 accumulation resulting from cprgs-1 gene deletion were also observed in a strain containing a mutationally activated copy of CPG-1 but not in strains containing constitutively activated mutant alleles of the other two identified Gα subunits, CPG-2 and CPG-3. Furthermore, cprgs-1 transcript levels were increased in the activated CPG-1 strain but were unaltered in activated CPG-2 and CPG-3 strains. The results strongly suggest that CPRGS-1 is involved in regulation of Gα subunit CPG-1-mediated signaling and establish a role for a RGS protein in the modulation of virulence, conidiation, and hydrophobin synthesis in a plant pathogenic fungus.

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