Carbon source induced yeast-to-hypha transition in Candida albicans is dependent on the presence of amino acids and on the G-protein-coupled receptor Gpr1

2005 ◽  
Vol 33 (1) ◽  
pp. 291-293 ◽  
Author(s):  
M.M. Maidan ◽  
J.M. Thevelein ◽  
P. Van Dijck
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Amino Acids ◽  
Candida Albicans ◽  
Carbon Source ◽  
G Protein ◽  
High Glucose ◽  
Glucose Concentration ◽  
G Protein Coupled Receptor ◽  
Hypha Formation ◽  
G Protein Coupled

Yeast-to-hypha transition in Candida albicans can be induced by a wide variety of factors, including specific nutrients. We have started to investigate the mechanism by which some of these nutrients may be sensed. The G-protein-coupled receptor Gpr1 is required for yeast-to-hypha transition on various solid hypha-inducing media. Recently we have shown induction of Gpr1 internalization by specific amino acids, e.g. methionine. This suggests a possible role for methionine as a ligand of CaGpr1. Here we show that there is a big variation in methionine-induced hypha formation depending on the type of carbon source present in the medium. In addition high glucose concentrations repress hypha formation whereas a concentration of 0.1%, which mimics the glucose concentration present in the bloodstream, results in maximal hypha formation. Hence, it remains unclear whether Gpr1 senses sugars, as in Saccharomyces cerevisiae, or specific amino acids like methionine.

scholarly journals Gpr1, a Putative G-Protein-Coupled Receptor, Regulates Morphogenesis and Hypha Formation in the Pathogenic Fungus Candida albicans

2004 ◽  
Vol 3 (4) ◽  
pp. 919-931 ◽  
Author(s):  
Takuya Miwa ◽  
Yukinobu Takagi ◽  
Makiko Shinozaki ◽  
Cheol-Won Yun ◽  
Wiley A. Schell ◽  
...  
Keyword(s):  
Candida Albicans ◽  
G Protein ◽  
Pathogenic Fungus ◽  
Glucose Sensing ◽  
Dependent Manner ◽  
G Protein Coupled Receptor ◽  
Epistasis Analysis ◽  
Hypha Formation ◽  
Mutant Strains ◽  
G Protein Coupled

ABSTRACT In response to various extracellular signals, the morphology of the human fungal pathogen Candida albicans switches from yeast to hypha form. Here, we report that GPR1 encoding a putative G-protein-coupled receptor and GPA2 encoding a Gα subunit are required for hypha formation and morphogenesis in C. albicans. Mutants lacking Gpr1 (gpr1/gpr1) or Gpa2 (gpa2/gpa2) are defective in hypha formation and morphogenesis on solid hypha-inducing media. These phenotypic defects in solid cultures are suppressed by exogenously added dibutyryl-cyclic AMP (dibutyryl-cAMP). Biochemical studies also reveal that GPR1 and GPA2 are required for a glucose-dependent increase in cellular cAMP. An epistasis analysis indicates that Gpr1 functions upstream of Gpa2 in the same signaling pathway, and a two-hybrid assay reveals that the carboxyl-terminal tail of Gpr1 interacts with Gpa2. Moreover, expression levels of HWP1 and ECE1, which are cAMP-dependent hypha-specific genes, are reduced in both mutant strains. These findings support a model that Gpr1, as well as Gpa2, regulates hypha formation and morphogenesis in a cAMP-dependent manner. In contrast, GPR1 and GPA2 are not required for hypha formation in liquid fetal bovine serum (FBS) medium. Furthermore, the gpr1 and the gpa2 mutant strains are fully virulent in a mouse infection. These findings suggest that Gpr1 and Gpa2 are involved in the glucose-sensing machinery that regulates morphogenesis and hypha formation in solid media via a cAMP-dependent mechanism, but they are not required for hypha formation in liquid medium or during invasive candidiasis.

scholarly journals The G Protein-Coupled Receptor Gpr1 Is a Nutrient Sensor That Regulates Pseudohyphal Differentiation in Saccharomyces cerevisiae

Genetics ◽  
2000 ◽  
Vol 154 (2) ◽  
pp. 609-622 ◽  
Author(s):  
Michael C Lorenz ◽  
Xuewen Pan ◽  
Toshiaki Harashima ◽  
Maria E Cardenas ◽  
Yong Xue ◽  
...  
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Carbon Source ◽  
Map Kinase ◽  
G Protein ◽  
Nitrogen Starvation ◽  
G Protein Coupled Receptor ◽  
Map Kinase Cascade ◽  
Kinase Cascade ◽  
Pseudohyphal Differentiation ◽  
G Protein Coupled

Abstract Pseudohyphal differentiation in the budding yeast Saccharomyces cerevisiae is induced in diploid cells in response to nitrogen starvation and abundant fermentable carbon source. Filamentous growth requires at least two signaling pathways: the pheromone responsive MAP kinase cascade and the Gpa2p-cAMP-PKA signaling pathway. Recent studies have established a physical and functional link between the Gα protein Gpa2 and the G protein-coupled receptor homolog Gpr1. We report here that the Gpr1 receptor is required for filamentous and haploid invasive growth and regulates expression of the cell surface flocculin Flo11. Epistasis analysis supports a model in which the Gpr1 receptor regulates pseudohyphal growth via the Gpa2p-cAMP-PKA pathway and independently of both the MAP kinase cascade and the PKA related kinase Sch9. Genetic and physiological studies indicate that the Gpr1 receptor is activated by glucose and other structurally related sugars. Because expression of the GPR1 gene is known to be induced by nitrogen starvation, the Gpr1 receptor may serve as a dual sensor of abundant carbon source (sugar ligand) and nitrogen starvation. In summary, our studies reveal a novel G protein-coupled receptor senses nutrients and regulates the dimorphic transition to filamentous growth via a Gα protein-cAMP-PKA signal transduction cascade.

scholarly journals Aromatic D-amino acids act as chemoattractant factors for human leukocytes through a G protein-coupled receptor, GPR109B

2009 ◽  
Vol 106 (10) ◽  
pp. 3930-3934 ◽  
Author(s):  
Y. Irukayama-Tomobe ◽  
H. Tanaka ◽  
T. Yokomizo ◽  
T. Hashidate-Yoshida ◽  
M. Yanagisawa ◽  
...  
Keyword(s):  
Amino Acids ◽  
G Protein ◽  
G Protein Coupled Receptor ◽  
Human Leukocytes ◽  
G Protein Coupled

scholarly journals Affinity purification and characterization of a G-protein coupled receptor, Saccharomyces cerevisiae Ste2p

2007 ◽  
Vol 56 (1) ◽  
pp. 62-71 ◽  
Author(s):  
Byung-Kwon Lee ◽  
Kyung-Sik Jung ◽  
Cagdas Son ◽  
Heejung Kim ◽  
Nathan C. VerBerkmoes ◽  
...  
Keyword(s):  
Saccharomyces Cerevisiae ◽  
G Protein ◽  
Affinity Purification ◽  
G Protein Coupled Receptor ◽  
Purification And Characterization ◽  
G Protein Coupled

scholarly journals Plasma Membrane and Nuclear Localization of G Protein–coupled Receptor Kinase 6A

2007 ◽  
Vol 18 (8) ◽  
pp. 2960-2969 ◽  
Author(s):  
Xiaoshan Jiang ◽  
Jeffrey L. Benovic ◽  
Philip B. Wedegaertner
Keyword(s):  
Amino Acids ◽  
Plasma Membrane ◽  
G Protein ◽  
Nuclear Localization ◽  
Nuclear Export ◽  
Amphipathic Helix ◽  
G Protein Coupled Receptor ◽  
C Terminus ◽  
Acidic Residues ◽  
G Protein Coupled

G protein–coupled receptor (GPCR) kinases (GRKs) specifically phosphorylate agonist-occupied GPCRs at the inner surface of the plasma membrane (PM), leading to receptor desensitization. Here we show that the C-terminal 30 amino acids of GRK6A contain multiple elements that either promote or inhibit PM localization. Disruption of palmitoylation by individual mutation of cysteine 561, 562, or 565 or treatment of cells with 2-bromopalmitate shifts GRK6A from the PM to both the cytoplasm and nucleus. Likewise, disruption of the hydrophobic nature of a predicted amphipathic helix by mutation of two leucines to alanines at positions 551 and 552 causes a loss of PM localization. Moreover, acidic amino acids in the C-terminus appear to negatively regulate PM localization; mutational replacement of several acidic residues with neutral or basic residues rescues PM localization of a palmitoylation-defective GRK6A. Last, we characterize the novel nuclear localization, showing that nuclear export of nonpalmitoylated GRK6A is sensitive to leptomycin B and that GRK6A contains a potential nuclear localization signal. Our results suggest that the C-terminus of GRK6A contains a novel electrostatic palmitoyl switch in which acidic residues weaken the membrane-binding strength of the amphipathic helix, thus allowing changes in palmitoylation to regulate PM versus cytoplasmic/nuclear localization.

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