Cyclic AMP pathway activation and extracellular zinc induce rapid intracellular zinc mobilization in Candida albicans

Lasse Kjellerup, Anne-Marie L. Winther, Duncan Wilson, Anja T. Fuglsang

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3 Citations (Scopus)
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Abstract

Zinc is an essential micronutrient, required for a range of zinc dependent enzymes and transcription factors. In mammalian cells, zinc serves as a second messenger molecule. However, a role for zinc in signaling has not yet been established in the fungal kingdom. Here, we used the intracellular zinc reporter, zinbo 5, which allowed visualization of zinc in the endoplasmic reticulum and other components of the internal membrane system in Candida albicans. We provide evidence for a link between cyclic AMP/PKA- and zinc- signaling in this major human fungal pathogen. Glucose stimulation, which triggers a cyclic AMP spike in this fungus resulted in rapid intracellular zinc mobilization and this “zinc flux” could be stimulated with phosphodiesterase inhibitors and blocked via inhibition of adenylate cyclase or PKA. A similar mobilization of intracellular zinc was generated by stimulation of cells with extracellular zinc and this effect could be reversed with the chelator EDTA. However zinc-induced zinc flux was found to be cyclic AMP independent. In summary, we show that activation of the cyclic AMP/PKA pathway triggers intracellular zinc mobilization in a fungus. To our knowledge, this is the first described link between cyclic AMP signaling and zinc homeostasis in a human fungal pathogen.
Original languageEnglish
Article number502
JournalFrontiers in Microbiology
Volume9
DOIs
Publication statusPublished - 21 Mar 2018

Fingerprint

Candida albicans
Cyclic AMP
Zinc
Fungi
Phosphodiesterase Inhibitors
Micronutrients
Second Messenger Systems
Chelating Agents
Adenylyl Cyclases
Edetic Acid
Endoplasmic Reticulum
Homeostasis
Transcription Factors

Keywords

  • cAMP Zinc
  • candida albicans
  • signaling
  • ER
  • ion homeostasis
  • bioimaging

Cite this

Cyclic AMP pathway activation and extracellular zinc induce rapid intracellular zinc mobilization in Candida albicans. / Kjellerup, Lasse ; Winther, Anne-Marie L. ; Wilson, Duncan; Fuglsang, Anja T.

In: Frontiers in Microbiology, Vol. 9, 502, 21.03.2018.

Research output: Contribution to journalArticle

Kjellerup, Lasse ; Winther, Anne-Marie L. ; Wilson, Duncan ; Fuglsang, Anja T. / Cyclic AMP pathway activation and extracellular zinc induce rapid intracellular zinc mobilization in Candida albicans. In: Frontiers in Microbiology. 2018 ; Vol. 9.
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abstract = "Zinc is an essential micronutrient, required for a range of zinc dependent enzymes and transcription factors. In mammalian cells, zinc serves as a second messenger molecule. However, a role for zinc in signaling has not yet been established in the fungal kingdom. Here, we used the intracellular zinc reporter, zinbo 5, which allowed visualization of zinc in the endoplasmic reticulum and other components of the internal membrane system in Candida albicans. We provide evidence for a link between cyclic AMP/PKA- and zinc- signaling in this major human fungal pathogen. Glucose stimulation, which triggers a cyclic AMP spike in this fungus resulted in rapid intracellular zinc mobilization and this “zinc flux” could be stimulated with phosphodiesterase inhibitors and blocked via inhibition of adenylate cyclase or PKA. A similar mobilization of intracellular zinc was generated by stimulation of cells with extracellular zinc and this effect could be reversed with the chelator EDTA. However zinc-induced zinc flux was found to be cyclic AMP independent. In summary, we show that activation of the cyclic AMP/PKA pathway triggers intracellular zinc mobilization in a fungus. To our knowledge, this is the first described link between cyclic AMP signaling and zinc homeostasis in a human fungal pathogen.",
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N1 - LK was supported by Innovation Fund Denmark, DK (4019-00019B). Pcovery ApS received funding from Wellcome Trust, Research Councils, UK (100480/Z/12), Novo Seeds, DK and Boehringer Ingelheim Venture Fund, D. DW is supported by a Sir Henry Dale Fellowship jointly funded by the Wellcome Trust and the Royal Society (102549/Z/13/Z), the Medical Research Council and University of Aberdeen (MR/N006364/1) and received support from a Wellcome Trust Strategic Award for Medical Mycology and Fungal Immunology (097377/Z/11/Z). The funders had no part in study design, data collection and interpretation, or the decision to submit the work for publication.

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N2 - Zinc is an essential micronutrient, required for a range of zinc dependent enzymes and transcription factors. In mammalian cells, zinc serves as a second messenger molecule. However, a role for zinc in signaling has not yet been established in the fungal kingdom. Here, we used the intracellular zinc reporter, zinbo 5, which allowed visualization of zinc in the endoplasmic reticulum and other components of the internal membrane system in Candida albicans. We provide evidence for a link between cyclic AMP/PKA- and zinc- signaling in this major human fungal pathogen. Glucose stimulation, which triggers a cyclic AMP spike in this fungus resulted in rapid intracellular zinc mobilization and this “zinc flux” could be stimulated with phosphodiesterase inhibitors and blocked via inhibition of adenylate cyclase or PKA. A similar mobilization of intracellular zinc was generated by stimulation of cells with extracellular zinc and this effect could be reversed with the chelator EDTA. However zinc-induced zinc flux was found to be cyclic AMP independent. In summary, we show that activation of the cyclic AMP/PKA pathway triggers intracellular zinc mobilization in a fungus. To our knowledge, this is the first described link between cyclic AMP signaling and zinc homeostasis in a human fungal pathogen.

AB - Zinc is an essential micronutrient, required for a range of zinc dependent enzymes and transcription factors. In mammalian cells, zinc serves as a second messenger molecule. However, a role for zinc in signaling has not yet been established in the fungal kingdom. Here, we used the intracellular zinc reporter, zinbo 5, which allowed visualization of zinc in the endoplasmic reticulum and other components of the internal membrane system in Candida albicans. We provide evidence for a link between cyclic AMP/PKA- and zinc- signaling in this major human fungal pathogen. Glucose stimulation, which triggers a cyclic AMP spike in this fungus resulted in rapid intracellular zinc mobilization and this “zinc flux” could be stimulated with phosphodiesterase inhibitors and blocked via inhibition of adenylate cyclase or PKA. A similar mobilization of intracellular zinc was generated by stimulation of cells with extracellular zinc and this effect could be reversed with the chelator EDTA. However zinc-induced zinc flux was found to be cyclic AMP independent. In summary, we show that activation of the cyclic AMP/PKA pathway triggers intracellular zinc mobilization in a fungus. To our knowledge, this is the first described link between cyclic AMP signaling and zinc homeostasis in a human fungal pathogen.

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