scholarly journals Role of Actin Cytoskeletal Dynamics in Activation of the Cyclic AMP Pathway and HWP1 Gene Expression in Candida albicans

2007 ◽  
Vol 6 (10) ◽  
pp. 1824-1840 ◽  
Author(s):  
Michael J. Wolyniak ◽  
Paula Sundstrom
Keyword(s):  
Gene Expression ◽  
Candida Albicans ◽  
Cyclic Amp ◽  
Signaling Pathway ◽  
Camp Signaling ◽  
Specific Gene ◽  
Camp Signaling Pathway ◽  
Hypha Formation ◽  
Cytoskeletal Dynamics ◽  
Opportunistic Fungal Pathogen

ABSTRACT Changes in gene expression during reversible bud-hypha transitions of the opportunistic fungal pathogen Candida albicans permit adaptation to environmental conditions that are critical for proliferation in host tissues. Our previous work has shown that the hypha-specific adhesin gene HWP1 is up-regulated by the cyclic AMP (cAMP) signaling pathway. However, little is known about the potential influences of determinants of cell morphology on HWP1 gene expression. We found that blocking hypha formation with cytochalasin A, which destabilizes actin filaments, and with latrunculin A, which sequesters actin monomers, led to a loss of HWP1 gene expression. In contrast, high levels of HWP1 gene expression were observed when the F-actin stabilizer jasplakinolide was used to block hypha formation, suggesting that HWP1 expression could be regulated by actin structures. Mutants defective in formin-mediated nucleation of F-actin were reduced in HWP1 gene expression, providing genetic support for the importance of actin structures. Kinetic experiments with wild-type and actin-deficient cells revealed two distinct phases of HWP1 gene expression, with a slow, actin-independent phase preceding a fast, actin-dependent phase. Low levels of HWP1 gene expression that appeared to be independent of stabilized actin and cAMP signaling were detected using indirect immunofluorescence. A connection between actin structures and the cAMP signaling pathway was shown using hyper- and hypomorphic cAMP mutants, providing a possible mechanism for up-regulation of HWP1 gene expression by stabilized actin. The results reveal a new role for F-actin as a regulatory agent of hypha-specific gene expression at the bud-hypha transition.

scholarly journals Genome-Wide Transcriptional Profiling of the Cyclic AMP-Dependent Signaling Pathway during Morphogenic Transitions of Candida albicans

2007 ◽  
Vol 6 (12) ◽  
pp. 2376-2390 ◽  
Author(s):  
Yong-Sun Bahn ◽  
Matthew Molenda ◽  
Janet F. Staab ◽  
Courtney A. Lyman ◽  
Laura J. Gordon ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Cyclic Amp ◽  
Signaling Pathway ◽  
Virulence Factors ◽  
Molecular Mechanisms ◽  
Nitrosative Stress ◽  
Camp Signaling ◽  
Phenotypic Traits ◽  
Null Mutant ◽  
Camp Signaling Pathway

ABSTRACT Candida albicans is an opportunistic human fungal pathogen that causes systemic candidiasis as well as superficial mucosal candidiasis. In response to the host environment, C. albicans transitions between yeast and hyphal forms. In particular, hyphal growth is important in facilitating adhesion and invasion of host tissues, concomitant with the expression of various hypha-specific virulence factors. In previous work, we showed that the cyclic AMP (cAMP) signaling pathway plays a crucial role in morphogenic transitions and virulence of C. albicans by studying genes encoding adenylate cyclase-associated protein (CAP1) and high-affinity phosphodiesterase (PDE2) (Y. S. Bahn, J. Staab, and P. Sundstrom, Mol. Microbiol. 50:391-409, 2003; and Y. S. Bahn and P. Sundstrom, J. Bacteriol. 183:3211-3223, 2001). However, little is known about the downstream targets of the cAMP signaling pathway that are responsible for morphological transitions and the expression of virulence factors. Here, microarrays were probed with RNA from strains with hypoactive (cap1/cap1 null mutant), hyperactive (pde2/pde2 null mutant), and wild-type cAMP signaling pathways to provide insight into the molecular mechanisms of virulence that are regulated by cAMP and that are related to the morphogenesis of C. albicans. Genes controlling metabolic specialization, cell wall structure, ergosterol/lipid biosynthesis, and stress responses were modulated by cAMP during hypha formation. Phenotypic traits predicted to be regulated by cAMP from the profiling results correlated with the relative strengths of the mutants when tested for resistance to azoles and subjected to heat shock stress and oxidative/nitrosative stress. The results from this study provide important insights into the role of the cAMP signaling pathway not only in morphogenic transitions of C. albicans but also for adaptation to stress and for survival during host infections.

scholarly journals Cyclic AMP Stimulates SF-1-Dependent CYP11A1 Expression through Homeodomain-Interacting Protein Kinase 3-Mediated Jun N-Terminal Kinase and c-Jun Phosphorylation

2007 ◽  
Vol 27 (6) ◽  
pp. 2027-2036 ◽  
Author(s):  
Hsin-Chieh Lan ◽  
Hua-Jung Li ◽  
Guang Lin ◽  
Pao-Yen Lai ◽  
Bon-chu Chung
Keyword(s):  
Gene Expression ◽  
Protein Kinase ◽  
Cyclic Amp ◽  
Signaling Pathway ◽  
Camp Signaling ◽  
Functional Interaction ◽  
Interacting Protein ◽  
Surface Receptors ◽  
Camp Signaling Pathway ◽  
Camp Stimulation

ABSTRACT Steroids are synthesized in adrenal glands and gonads under the control of pituitary peptides. These peptides bind to cell surface receptors to activate the cyclic AMP (cAMP) signaling pathway leading to an increase of steroidogenic gene expression. Exactly how cAMP activates steroidogenic gene expression is not clear, except for the knowledge that transcription factor SF-1 plays a key role. Investigating the factors participating in SF-1 action, we found that c-Jun and homeodomain-interacting protein kinase 3 (HIPK3) were required for basal and cAMP-stimulated expression of one major steroidogenic gene, CYP11A1. HIPK3 enhanced SF-1 activity, and c-Jun was required for the functional interaction of HIPK3 with SF-1. Furthermore, after cAMP stimulation, both c-Jun and Jun N-terminal kinase (JNK) were phosphorylated through HIPK3. These phosphorylations were important for SF-1 activity and CYP11A1 expression. Thus, we have defined HIPK3-mediated JNK activity and c-Jun phosphorylation as important events that increase SF-1 activity for CYP11A1 transcription in response to cAMP. This finding has linked three common factors, HIPK3, JNK, and c-Jun, to the cAMP signaling pathway leading to increased steroidogenic gene expression.

scholarly journals CAP1, an Adenylate Cyclase-Associated Protein Gene, Regulates Bud-Hypha Transitions, Filamentous Growth, and Cyclic AMP Levels and Is Required for Virulence of Candida albicans

2001 ◽  
Vol 183 (10) ◽  
pp. 3211-3223 ◽  
Author(s):  
Yong-Sun Bahn ◽  
Paula Sundstrom
Keyword(s):  
Candida Albicans ◽  
Cyclic Amp ◽  
Adenylate Cyclase ◽  
Germ Tube ◽  
Filamentous Growth ◽  
Tube Formation ◽  
Camp Signaling ◽  
Solid Media ◽  
Opportunistic Fungal Pathogen ◽  
Camp Levels

ABSTRACT In response to a wide variety of environmental stimuli, the opportunistic fungal pathogen Candida albicans exits the budding cycle, producing germ tubes and hyphae concomitant with expression of virulence genes, such as that encoding hyphal wall protein 1 (HWP1). Biochemical studies implicate cyclic AMP (cAMP) increases in promoting bud-hypha transitions, but genetic evidence relating genes that control cAMP levels to bud-hypha transitions has not been reported. Adenylate cyclase-associated proteins (CAPs) of nonpathogenic fungi interact with Ras and adenylate cyclase to increase cAMP levels under specific environmental conditions. To initiate studies on the relationship between cAMP signaling and bud-hypha transitions in C. albicans, we identified, cloned, characterized, and disrupted the C. albicans CAP1 gene. C. albicans strains with inactivated CAP1 budded in conditions that led to germ tube formation in isogenic strains withCAP1. The addition of 10 mM cAMP and dibutyryl cAMP promoted bud-hypha transitions and filamentous growth in thecap1/cap1 mutant in liquid and solid media, respectively, showing clearly that cAMP promotes hypha formation in C. albicans. Increases in cytoplasmic cAMP preceding germ tube emergence in strains having CAP1 were markedly diminished in the budding cap1/cap1 mutant. C. albicans strains with deletions of both alleles ofCAP1 were avirulent in a mouse model of systemic candidiasis. The avirulence of a germ tube-deficientcap1/cap1 mutant coupled with the role of Cap1 in regulating cAMP levels shows that the Cap1-mediated cAMP signaling pathway is required for bud-hypha transitions, filamentous growth, and the pathogenesis of candidiasis.

scholarly journals Mechanistic Differences in the Activation of Estrogen Receptor-α (ERα)- and ERβ-dependent Gene Expression by cAMP Signaling Pathway(s)

2003 ◽  
Vol 278 (15) ◽  
pp. 12834-12845 ◽  
Author(s):  
Kevin M. Coleman ◽  
Martin Dutertre ◽  
Abeer El-Gharbawy ◽  
Brian G. Rowan ◽  
Nancy L. Weigel ◽  
...  
Keyword(s):  
Gene Expression ◽  
Estrogen Receptor ◽  
Signaling Pathway ◽  
Estrogen Receptor Α ◽  
Camp Signaling ◽  
Camp Signaling Pathway

scholarly journals cAMP signaling pathway controls glycogen metabolism in Neurospora crassa by regulating the glycogen synthase gene expression and phosphorylation

2010 ◽  
Vol 47 (1) ◽  
pp. 43-52 ◽  
Author(s):  
Fernanda Zanolli Freitas ◽  
Renato Magalhães de Paula ◽  
Luiz Carlos Bertucci Barbosa ◽  
Hector Francisco Terenzi ◽  
Maria Célia Bertolini
Keyword(s):  
Gene Expression ◽  
Neurospora Crassa ◽  
Signaling Pathway ◽  
Glycogen Synthase ◽  
Glycogen Metabolism ◽  
Camp Signaling ◽  
Camp Signaling Pathway

scholarly journals Msn2p and Msn4p Control a Large Number of Genes Induced at the Diauxic Transition Which Are Repressed by Cyclic AMP inSaccharomyces cerevisiae

1998 ◽  
Vol 180 (5) ◽  
pp. 1044-1052 ◽  
Author(s):  
Emmanuelle Boy-Marcotte ◽  
Michel Perrot ◽  
Françoise Bussereau ◽  
Hélian Boucherie ◽  
Michel Jacquet
Keyword(s):  
Cyclic Amp ◽  
Signaling Pathway ◽  
Camp Signaling ◽  
Exponential Growth Phase ◽  
Diauxic Shift ◽  
Two Dimensional Gel Electrophoresis ◽  
Control Of Gene Expression ◽  
Camp Signaling Pathway ◽  
Number Of Genes ◽  
Multicopy Suppressors

ABSTRACT The multicopy suppressors of the snf1 defect, Msn2p and Msn4p transcription factors (Msn2/4p), activate genes through the stress-responsive cis element (CCCCT) in response to various stresses. This cis element is also the target for repression by the cyclic AMP (cAMP)-signaling pathway. We analyzed the two-dimensional gel electrophoresis pattern of protein synthesis of themsn2 msn4 double mutant and compared it with that of the wild-type strain during exponential growth phase and at the diauxic transition. Thirty-nine gene products (including those ofALD3, GDH3, GLK1, GPP2,HSP104, HXK1, PGM2,SOD2, SSA3, SSA4, TKL2,TPS1, and YBR149W) are dependent upon Msn2/4p for their induction at the diauxic transition. The expression of all these genes is repressed by cAMP. Thirty other genes identified during this study are still inducible in the mutant. A subset of these genes were found to be superinduced at the diauxic transition, and others were subject to cAMP repression (including ACH1,ADH2, ALD6, ATP2, GPD1,ICL1, and KGD2). We conclude from this analysis that Msn2/4p control a large number of genes induced at the diauxic transition but that other, as-yet-uncharacterized regulators, also contribute to this response. In addition, we show here that cAMP repression applies to both Msn2/4p-dependent and -independent control of gene expression at the diauxic shift. Furthermore, the fact that all the Msn2/4p gene targets are subject to cAMP repression suggests that these regulators could be targets for the cAMP-signaling pathway.

scholarly journals Role of cyclic AMP in the control of cell-specific gene expression

1993 ◽  
Vol 4 (6) ◽  
pp. 204-209 ◽  
Author(s):  
Wolfgang Schmid ◽  
Doris Nitsch ◽  
Michael Boshart ◽  
Günther Schütz
Keyword(s):  
Gene Expression ◽  
Cyclic Amp ◽  
Specific Gene ◽  
Specific Gene Expression

scholarly journals Role of cAMP in Double Switch of Glucagon Secretion

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 896
Author(s):  
Jan Zmazek ◽  
Vladimir Grubelnik ◽  
Rene Markovič ◽  
Marko Marhl
Keyword(s):  
Glucose Metabolism ◽  
Signaling Pathway ◽  
Cell Model ◽  
Dominant Role ◽  
Glucagon Secretion ◽  
Camp Signaling ◽  
Independent Manner ◽  
Metabolic Switch ◽  
Camp Signaling Pathway ◽  
Double Switch

Glucose metabolism plays a crucial role in modulating glucagon secretion in pancreatic alpha cells. However, the downstream effects of glucose metabolism and the activated signaling pathways influencing glucagon granule exocytosis are still obscure. We developed a computational alpha cell model, implementing metabolic pathways of glucose and free fatty acids (FFA) catabolism and an intrinsically activated cAMP signaling pathway. According to the model predictions, increased catabolic activity is able to suppress the cAMP signaling pathway, reducing exocytosis in a Ca2+-dependent and Ca2+ independent manner. The effect is synergistic to the pathway involving ATP-dependent closure of KATP channels and consequent reduction of Ca2+. We analyze the contribution of each pathway to glucagon secretion and show that both play decisive roles, providing a kind of “secure double switch”. The cAMP-driven signaling switch plays a dominant role, while the ATP-driven metabolic switch is less favored. The ratio is approximately 60:40, according to the most recent experimental evidence.

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