Affiliation:
1. Jiangsu Key Laboratory for Microbes and Functional Genomics, Engineering and Technology Research Center for Microbiology, College of Life Sciences, Nanjing Normal University , Nanjing, Jiangsu, China
2. Department of Bioinformatics, School of Life Sciences, Xuzhou Medical University , Xuzhou, Jiangsu, China
Abstract
ABSTRACT
The maintenance of cellular calcium homeostasis in response to calcium supply is required for a wide range of physiological processes in fungi, including growth, development, and virulence. In
Aspergillus
, the transcription factor CrzA is involved in efficient regulation of calcium homeostasis, especially under calcium-repleted conditions. However, the transcriptional regulatory mechanisms under calcium-limited conditions remain unclear. Here, we found that a highly conserved transcription factor, SltA, known for its roles in salt tolerance and azole resistance, can confer adaptation to calcium-limited conditions in
Aspergillus fumigatus
. Loss of
sltA
caused severe growth defects with abnormal expressions of calcium metabolism-related genes, which resulted in a decreased cytosolic calcium transient under calcium-limited conditions, while the addition of calcium rescued all defective phenotypes in the Δ
sltA
mutant. Moreover,
A. fumigatus
SltA undergoes a proteolysis modification that depends on SltB, a chymotrypsin-like serine protease. Strikingly,
A. fumigatus
SltA plays a reverse role to CrzA in the regulation of expressions of calcium metabolism-related genes. Deletion of
crzA
significantly suppressed the growth defect of the Δ
sltA
mutant. Deletion of
sltA
led to highly expressed CrzA with a constant nuclear location under calcium-limited conditions, demonstrating that there exists a mutually restricted network regulated by SltA and CrzA to adapt to calcium-limited conditions. Electrophoretic mobility shift assays and chromatin immunoprecipitation sequencing revealed that SltA directly binds to a subset of genes involved in calcium metabolism via a conserved motif. These findings expand knowledge on the regulatory circuits of the Ca
2+
signaling pathway.
IMPORTANCE
Calcium ions are ubiquitous intracellular signaling molecules for many signaling pathways regulating the fungal response to stress and antifungal drugs. The concentration of intracellular calcium is tightly regulated in its storage, release, and distribution. CrzA is the best-studied transcription factor that regulates this process under sufficient calcium or other external signals. However, CrzA was excluded from nuclei and then lost transcriptional activation under calcium-limited conditions. The regulators in the Ca
2+
signaling pathway under calcium-limited conditions remain unclear. Here, we identified SltA as a key regulator in the Ca
2+
signaling pathway under calcium-limited conditions, and the underlying mechanisms were further explored in
Aspergillus fumigatus
. These findings reveal a transcriptional control pathway that precisely regulates calcium homeostasis under calcium-limited conditions.
Funder
MOST | National Natural Science Foundation of China
Priority Academic Program Development of Jiangsu Higher Education Institutions
Publisher
American Society for Microbiology
Subject
Ecology,Applied Microbiology and Biotechnology,Food Science,Biotechnology
Cited by
2 articles.
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