Candida albicans Cyr1, Cap1 and G-actin form a sensor/effector apparatus for activating cAMP synthesis in hyphal growth.
A key virulence trait of Candida albicans is its ability to undergo the yeast-to-hyphal growth transition in response to environmental signals. This transition critically requires a rapid activation of the adenylyl cyclase Cyr1 to generate a cAMP spike. However, the identity of the signal sensors and mechanisms of signal processing and integration remain largely unclear. Recent evidence suggests that some sensors are embedded in Cyr1 itself. To test this hypothesis, we asked whether purified Cyr1 can respond to hyphal induction. Here, we report that Cyr1 co-purifies with Cap1 and G-actin as a tripartite complex which can increase cAMP synthesis in response to hyphal inducing signals in an actin-dependent manner. Cap1 binds Cyr1 and G-actin through its N- and C-terminus respectively. Deleting the G-actin binding sites or treating the complex with the actin toxin latrunculin A or cytochalasin A inhibits the activation of cAMP synthesis. Strains expressing Cap1 mutants lacking the G-actin binding site are impaired in both cAMP synthesis and hyphal morphogenesis. Thus, our findings reveal an essentially intact sensor/effector apparatus composed of Cyr1, Cap1 and G-actin. Furthermore, G-actin's regulatory role in this apparatus may prove to be the missing link whereby cellular actin status knowingly influences cAMP-mediated cellular processes.
Zou
Hao
H
Institute of Molecular and Cell Biology, A *STAR (Agency for Science, Technology and Research), 61 Biopolis Drive, Singapore 138673, Singapore.
Fang
Hao-Ming
HM
Zhu
Yong
Y
Wang
Yue
Y
D000199:Actins / Q000378:metabolism*; D000262:Adenylyl Cyclases / Q000378:metabolism*; D050976:Basic-Leucine Zipper Transcription Factors; D002176:Candida albicans / Q000201:enzymology / Q000254:growth & development / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000378:metabolism*; D000242:Cyclic AMP / Q000096:biosynthesis*; D005656:Fungal Proteins / Q000378:metabolism*; D025301:Hyphae / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D015398:Signal Transduction
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