Adenylyl cyclase-associated protein Aca1 regulates virulence and differentiation of Cryptococcus neoformans via the cyclic AMP-protein kinase A cascade

Yong Sun Bahn, Julie K. Hicks, Steven S. Giles, Gary M. Cox, Joseph Heitman

Research output: Contribution to journalArticle

88 Citations (Scopus)

Abstract

The evolutionarily conserved cyclic AMP (cAMP) signaling pathway controls cell functions in response to environmental cues in organisms as diverse as yeast and mammals. In the basidiomycetous human pathogenic fungus Cryptococcus neoformans, the cAMP pathway governs virulence and morphological differentiation. Here we identified and characterized adenylyl cyclase-associated protein, Aca1, which functions in parallel with the Gα subunit Gpa1 to control the adenylyl cyclase (Cac1). Aca1 interacted with the C terminus of Cac1 in the yeast two-hybrid system. By molecular and genetic approaches, Aca1 was shown to play a critical role in mating by regulating cell fusion and filamentous growth in a cAMP-dependent manner. Aca1 also regulates melanin and capsule production via the Cac1-cAMP-protein kinase A pathway. Genetic epistasis studies support models in which Aca1 and Gpa1 are necessary and sufficient components that cooperate to activate adenylyl cyclase. Taken together, these studies further define the cAMP signaling cascade controlling virulence of this ubiquitous human fungal pathogen.

Original languageEnglish
Pages (from-to)1476-1491
Number of pages16
JournalEukaryotic Cell
Volume3
Issue number6
DOIs
Publication statusPublished - 2004 Dec 1

Fingerprint

Adenylate Kinase
Cryptococcus neoformans
Cyclic AMP-Dependent Protein Kinases
Adenylyl Cyclases
Cyclic AMP
Virulence
Proteins
Genetic Epistasis
Two-Hybrid System Techniques
Cell Fusion
Melanins
Capsules
Cues
Molecular Biology
Mammals
Fungi
Yeasts
Growth

All Science Journal Classification (ASJC) codes

  • Microbiology
  • Molecular Biology

Cite this

@article{6076c32c85ad44028fdd85b9d6a2292a,
title = "Adenylyl cyclase-associated protein Aca1 regulates virulence and differentiation of Cryptococcus neoformans via the cyclic AMP-protein kinase A cascade",
abstract = "The evolutionarily conserved cyclic AMP (cAMP) signaling pathway controls cell functions in response to environmental cues in organisms as diverse as yeast and mammals. In the basidiomycetous human pathogenic fungus Cryptococcus neoformans, the cAMP pathway governs virulence and morphological differentiation. Here we identified and characterized adenylyl cyclase-associated protein, Aca1, which functions in parallel with the Gα subunit Gpa1 to control the adenylyl cyclase (Cac1). Aca1 interacted with the C terminus of Cac1 in the yeast two-hybrid system. By molecular and genetic approaches, Aca1 was shown to play a critical role in mating by regulating cell fusion and filamentous growth in a cAMP-dependent manner. Aca1 also regulates melanin and capsule production via the Cac1-cAMP-protein kinase A pathway. Genetic epistasis studies support models in which Aca1 and Gpa1 are necessary and sufficient components that cooperate to activate adenylyl cyclase. Taken together, these studies further define the cAMP signaling cascade controlling virulence of this ubiquitous human fungal pathogen.",
author = "Bahn, {Yong Sun} and Hicks, {Julie K.} and Giles, {Steven S.} and Cox, {Gary M.} and Joseph Heitman",
year = "2004",
month = "12",
day = "1",
doi = "10.1128/EC.3.6.1476-1491.2004",
language = "English",
volume = "3",
pages = "1476--1491",
journal = "Eukaryotic Cell",
issn = "1535-9778",
publisher = "American Society for Microbiology",
number = "6",

}

Adenylyl cyclase-associated protein Aca1 regulates virulence and differentiation of Cryptococcus neoformans via the cyclic AMP-protein kinase A cascade. / Bahn, Yong Sun; Hicks, Julie K.; Giles, Steven S.; Cox, Gary M.; Heitman, Joseph.

In: Eukaryotic Cell, Vol. 3, No. 6, 01.12.2004, p. 1476-1491.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Adenylyl cyclase-associated protein Aca1 regulates virulence and differentiation of Cryptococcus neoformans via the cyclic AMP-protein kinase A cascade

AU - Bahn, Yong Sun

AU - Hicks, Julie K.

AU - Giles, Steven S.

AU - Cox, Gary M.

AU - Heitman, Joseph

PY - 2004/12/1

Y1 - 2004/12/1

N2 - The evolutionarily conserved cyclic AMP (cAMP) signaling pathway controls cell functions in response to environmental cues in organisms as diverse as yeast and mammals. In the basidiomycetous human pathogenic fungus Cryptococcus neoformans, the cAMP pathway governs virulence and morphological differentiation. Here we identified and characterized adenylyl cyclase-associated protein, Aca1, which functions in parallel with the Gα subunit Gpa1 to control the adenylyl cyclase (Cac1). Aca1 interacted with the C terminus of Cac1 in the yeast two-hybrid system. By molecular and genetic approaches, Aca1 was shown to play a critical role in mating by regulating cell fusion and filamentous growth in a cAMP-dependent manner. Aca1 also regulates melanin and capsule production via the Cac1-cAMP-protein kinase A pathway. Genetic epistasis studies support models in which Aca1 and Gpa1 are necessary and sufficient components that cooperate to activate adenylyl cyclase. Taken together, these studies further define the cAMP signaling cascade controlling virulence of this ubiquitous human fungal pathogen.

AB - The evolutionarily conserved cyclic AMP (cAMP) signaling pathway controls cell functions in response to environmental cues in organisms as diverse as yeast and mammals. In the basidiomycetous human pathogenic fungus Cryptococcus neoformans, the cAMP pathway governs virulence and morphological differentiation. Here we identified and characterized adenylyl cyclase-associated protein, Aca1, which functions in parallel with the Gα subunit Gpa1 to control the adenylyl cyclase (Cac1). Aca1 interacted with the C terminus of Cac1 in the yeast two-hybrid system. By molecular and genetic approaches, Aca1 was shown to play a critical role in mating by regulating cell fusion and filamentous growth in a cAMP-dependent manner. Aca1 also regulates melanin and capsule production via the Cac1-cAMP-protein kinase A pathway. Genetic epistasis studies support models in which Aca1 and Gpa1 are necessary and sufficient components that cooperate to activate adenylyl cyclase. Taken together, these studies further define the cAMP signaling cascade controlling virulence of this ubiquitous human fungal pathogen.

UR - http://www.scopus.com/inward/record.url?scp=11144276482&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=11144276482&partnerID=8YFLogxK

U2 - 10.1128/EC.3.6.1476-1491.2004

DO - 10.1128/EC.3.6.1476-1491.2004

M3 - Article

C2 - 15590822

AN - SCOPUS:11144276482

VL - 3

SP - 1476

EP - 1491

JO - Eukaryotic Cell

JF - Eukaryotic Cell

SN - 1535-9778

IS - 6

ER -