The G Protein-coupled Receptor Gpr1 and the Gα Protein Gpa2 Act through the cAMP-Protein Kinase A Pathway to Induce Morphogenesis in<i>Candida albicans</i>

Maidan, Mykola; Rop, Larissa De; Serneels, Joke; Exler, Simone; Rupp, Steffen; Tournu, Hélène; Thevelein, Johan M.; Dijck, Patrick Van

doi:10.1091/mbc.e04-09-0780

Cited by 181 publications

(232 citation statements)

References 74 publications

(103 reference statements)

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“…CO 2 /HCO 3 2 directly stimulates Cyr1p activity by binding to the catalytic domain of Cyr1 (Klengel et al 2005). The cyclase activity is also regulated by the small GTPases (Ras1, Ras2), G-protein coupled receptor Gpr1, and Ga protein Gpa2 in response to nutrients (Feng et al 1999;Sanchez-Martinez and PerezMartin 2002;Miwa et al 2004;Maidan et al 2005a;Zhu et al 2009). Gpr1 in C. albicans is responsive to methionine, but not to glucose (Maidan et al 2005b), suggesting that this signal is likely encountered by this fungus in vivo.…”

Section: Environmental Regulation Of Hyphal Morphogenesis Sensing Nutmentioning

confidence: 99%

Fungal Morphogenesis

Lin

Alspaugh

Liu

et al. 2014

Cold Spring Harbor Perspectives in Medicine

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Morphogenesis in fungi is often induced by extracellular factors and executed by fungal genetic factors. Cell surface changes and alterations of the microenvironment often accompany morphogenetic changes in fungi. In this review, we will first discuss the general traits of yeast and hyphal morphotypes and how morphogenesis affects development and adaptation by fungi to their native niches, including host niches. Then we will focus on the molecular machinery responsible for the two most fundamental growth forms, yeast and hyphae. Last, we will describe how fungi incorporate exogenous environmental and host signals together with genetic factors to determine their morphotype and how morphogenesis, in turn, shapes the fungal microenvironment. PROPERTIES OF MORPHOGENESIS IN FUNGAL CELLS

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Section: Environmental Regulation Of Hyphal Morphogenesis Sensing Nutmentioning

confidence: 99%

Fungal Morphogenesis

Lin

Alspaugh

Liu

et al. 2014

Cold Spring Harbor Perspectives in Medicine

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“…The adenylate cyclase Cdc35 and its associated protein Cap1 are required for hyphal development under all hyphal-inducing conditions, including serum (Bahn and Sundstrom, 2001;Rocha et al, 2001). The cyclase activity is regulated by two G proteins, Ras1 and Gpa2, in C. albicans (Feng et al, 1999;Sanchez-Martinez and Perez-Martin, 2002;Miwa et al, 2004;Maidan et al, 2005). ras1 mutants are defective for hyphal formation under induction with serum filtrate in liquid media (Feng et al, 1999), whereas gpa2 mutants are defective in hyphal growth on solid hyphal-inducing media (Miwa et al, 2004;Maidan et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

“…The cyclase activity is regulated by two G proteins, Ras1 and Gpa2, in C. albicans (Feng et al, 1999;Sanchez-Martinez and Perez-Martin, 2002;Miwa et al, 2004;Maidan et al, 2005). ras1 mutants are defective for hyphal formation under induction with serum filtrate in liquid media (Feng et al, 1999), whereas gpa2 mutants are defective in hyphal growth on solid hyphal-inducing media (Miwa et al, 2004;Maidan et al, 2005). The G proteins act through PKA to induce morphogenesis in C. albicans.…”

Section: Introductionmentioning

confidence: 99%

The Flo8 Transcription Factor Is Essential for Hyphal Development and Virulence inCandida albicans

Cao

Lane

Raniga

et al. 2006

MBoC

196

255

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The transcription factor Flo8 is essential for filamentous growth in Saccharomyces cerevisiae and is regulated under the cAMP/protein kinase A (PKA) pathway. To determine whether a similar pathway/regulation exists in Candida albicans, we have cloned C. albicans FLO8 by its ability to complement S. cerevisiae flo8. Deleting FLO8 in C. albicans blocked hyphal development and hypha-specific gene expression. The flo8/flo8 mutant is avirulent in a mouse model of systemic infection. Genome-wide transcription profiling of efg1/efg1 and flo8/flo8 using a C. albicans DNA microarray suggests that Flo8 controls subsets of Efg1-regulated genes. Most of these genes are hypha specific, including HGC1 and IHD1. We also show that Flo8 interacts with Efg1 in yeast and hyphal cells by in vivo immunoprecipitation. Similar to efg1/efg1, flo8/flo8 and cdc35/cdc35 show enhanced hyphal growth under an embedded growth condition. Our results suggest that Flo8 may function downstream of the cAMP/PKA pathway, and together with Efg1, regulates the expression of hypha-specific genes and genes that are important for the virulence of C. albicans.

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“…One of the strongest known inducers of hyphal growth is serum. Screens for chemically defined inducers have found that nutrients, such as the amino sugar GlcNAc (Simonetti et al, 1974) and certain amino acids (Odds, 1988;Maidan et al, 2005), will also stimulate hyphal growth. Environmental conditions also contribute to hyphal induction, as it occurs optimally at 37°C and can be stimulated by alkaline pH and 5% CO 2 (Davis, 2003;Sudbery et al, 2004;Klengel et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

Identification of anN-Acetylglucosamine Transporter That Mediates Hyphal Induction inCandida albicans

Álvarez

Konopka

2007

MBoC

124

171

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The sugar N-acetylglucosamine (GlcNAc) plays an important role in nutrient sensing and cellular regulation in a wide range of organisms from bacteria to humans. In the fungal pathogen Candida albicans, GlcNAc induces a morphological transition from budding to hyphal growth. Proteomic comparison of plasma membrane proteins from buds and from hyphae induced by GlcNAc identified a novel hyphal protein (Ngt1) with similarity to the major facilitator superfamily of transporters. An Ngt1-GFP fusion was detected in the plasma membrane after induction with GlcNAc, but not other related sugars. Ngt1-GFP was also induced by macrophage phagocytosis, suggesting a role for the GlcNAc response in signaling entry into phagolysosomes. NGT1 is needed for efficient GlcNAc uptake and for the ability to induce hyphae at low GlcNAc concentrations. High concentrations of GlcNAc could bypass the need for NGT1 to induce hyphae, indicating that elevated intracellular levels of GlcNAc induce hyphal formation. Expression of NGT1 in Saccharomyces cerevisiae promoted GlcNAc uptake, indicating that Ngt1 acts directly as a GlcNAc transporter. Transport mediated by Ngt1 was specific, as other sugars could not compete for the uptake of GlcNAc. Thus, Ngt1 represents the first eukaryotic GlcNAc transporter to be discovered. The presence of NGT1 homologues in the genome sequences of a wide range of eukaryotes from yeast to mammals suggests that they may also function in the cellular processes regulated by GlcNAc, including those that underlie important diseases such as cancer and diabetes. INTRODUCTIONN-acetylglucosamine (GlcNAc) is an amino sugar that carries out important roles in a broad range of cells from bacteria to humans. One aspect of GlcNAc function is to mediate cellular signaling. In bacteria, GlcNAc induces components that are important for colonization of human hosts, including fimbrins that mediate adhesion to host cells (Sohanpal et al., 2004), multidrug exporter genes (Hirakawa et al., 2006) and Curli fibers that promote biofilm formation (Barnhart et al., 2006). In mammals, GlcNAc is a key sensor of nutrient status that is involved in insulin signaling, cell cycle control, and other essential processes. Nutritional effects that lead to increased GlcNAc levels result in its conversion to UDP-GlcNAc and subsequent attachment to proteins on serine or threonine residues in a dynamic manner that is analogous to modification of proteins by phosphorylation (Slawson and Hart, 2003;Zachara and Hart, 2006). In fact, the interplay between O-GlcNAc modification and phosphorylation of proteins regulates many critical transcription factors, such as c-myc and p53 (Chou and Hart, 2001;Yang et al., 2006). O-GlcNAc modification also regulates other processes including proteosome function (Zachara and Hart, 2004). In addition to these regulatory roles, GlcNAc contributes to the N-linked glycosylation, glycophosphatidylinositol (GPI) anchor addition to proteins and is polymerized into chitin, which forms part of the fungal cell wall and the exoskele...

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The G Protein-coupled Receptor Gpr1 and the Gα Protein Gpa2 Act through the cAMP-Protein Kinase A Pathway to Induce Morphogenesis inCandida albicans

Cited by 181 publications

References 74 publications

Fungal Morphogenesis

Fungal Morphogenesis

The Flo8 Transcription Factor Is Essential for Hyphal Development and Virulence inCandida albicans

Identification of anN-Acetylglucosamine Transporter That Mediates Hyphal Induction inCandida albicans

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