title: Linking cellular actin status with cAMP signaling in Candida albicans.
abstract: The fungal pathogen Candida albicans has a remarkable ability to switch growth forms. Particularly, the yeast-to-hyphae switch is closely linked with its virulence. A range of chemicals and conditions can promote hyphal growth including serum, peptidoglycan, CO2, neutral pH, and elevated temperature. All these signals act essentially through the adenylyl cyclase Cyr1 that synthesizes cAMP. Cells lacking Cyr1 are completely defective in hyphal growth. Recently, cellular actin status is found to influence cAMP synthesis. However, how Cyr1 senses and processes multiple external and internal signals to produce a contextually proper level of cAMP remains unclear. We hypothesized that Cyr1 itself possesses multiple sensors for different signals and achieves signal integration through a combined allosteric effect on the catalytic center. To test this hypothesis, we affinity-purified a Cyr1-containing complex and found that it could enhance cAMP synthesis upon treatment with serum, peptidoglycan or CO2 in vitro. The data indicate that the complex is an essentially intact sensor/effector apparatus for cAMP synthesis. The complex contains two more subunits, the cyclase-associated protein Cap1 and G-actin. We discovered that G-actin plays a regulatory role, rendering cAMP synthesis responsive to actin dynamics. These findings shed new lights on the mechanisms that regulate cAMP-mediated responses in fungi.
authors.affiliation: Institute of Molecular and Cell Biology, Agency for Science, Technology and Research, Singapore. mcbwangy@imcb.a-star.edu.sg
authors.forename: Yue
authors.initials: Y
authors.lastname: Wang
authors.forename: Hao
authors.initials: H
authors.lastname: Zou
authors.forename: Hao-Ming
authors.initials: HM
authors.lastname: Fang
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhu
mesh_terms: D000199:Actins / Q000378:metabolism*; D000262:Adenylyl Cyclases / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D050976:Basic-Leucine Zipper Transcription Factors; D002176:Candida albicans / Q000235:genetics / Q000254:growth & development* / Q000378:metabolism / Q000472:pathogenicity; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D000242:Cyclic AMP / Q000235:genetics / Q000378:metabolism*; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D015966:Gene Expression Regulation, Fungal; D025301:Hyphae / Q000235:genetics / Q000254:growth & development / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D000199:Actins; D050976:Basic-Leucine Zipper Transcription Factors; C426523:CAP1 protein, Candida albicans; D018797:Cell Cycle Proteins; D005656:Fungal Proteins; D000242:Cyclic AMP; D000262:Adenylyl Cyclases