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Calcineurin phosphatase in signal transduction: lessons from fission yeast
Reiko Sugiura1, Susie O Sio, Hisato Shuntoh
1Division of Molecular Pharmacology and Pharmacogenomics, Department of Genome Sciences, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan.
Abstract:
Calcineurin (protein phosphatase 2B), the only serine/threonine phosphatase under the control of Ca2+/calmodulin, is an important mediator in signal transmission, connecting the Ca2+-dependent signalling to a wide variety of cellular responses. Furthermore, calcineurin is specifically inhibited by the immunosuppressant drugs cyclosporin A and tacrolimus (FK506), and these drugs have been a powerful tool for identifying many of the roles of calcineurin. Calcineurin is enriched in the neural tissues, and also distributes broadly in other tissues. The structure of the protein is highly conserved from yeast to man. The combined use of powerful genetics and of specific calcineurin inhibitors in fission yeast Schizosaccharomyces pombe (S. pombe) identified new components of the calcineurin pathway, and defined new roles of calcineurin in the regulation of the many cellular processes. Recent data has revealed functional interactions in which calcineurin phosphatase is involved, such as the cross-talk between the Pmk1 MAP kinase signalling, or the PI signalling. Calcineurin also participates in membrane traffic and cytokinesis of fission yeast through its functional connection with members of the small GTPase Rab/Ypt family, and Type II myosin, respectively. These findings highlight the potential of fission yeast genetic studies to elucidate conserved elements of signal transduction cascades.
Insights
Calcineurin, a key calcium-dependent phosphatase, regulates cellular responses and is inhibited by immunosuppressants. Fission yeast studies reveal new calcineurin pathway components and roles in signaling, membrane traffic, and cytokinesis.
Area of Science:
- Cellular Biology
- Molecular Biology
- Biochemistry
Background:
- Calcineurin (protein phosphatase 2B) is a crucial Ca2+/calmodulin-dependent enzyme mediating signal transduction.
- It is conserved across species and enriched in neural tissues.
- Immunosuppressants like cyclosporin A and tacrolimus (FK506) are specific calcineurin inhibitors.
Purpose of the Study:
- To identify new components and roles of the calcineurin pathway using fission yeast genetics.
- To elucidate conserved elements of calcineurin-mediated signal transduction cascades.
Main Methods:
- Utilized powerful genetics in fission yeast (Schizosaccharomyces pombe).
- Employed specific calcineurin inhibitors (cyclosporin A, tacrolimus).
Main Results:
- Identified novel components of the calcineurin pathway in S. pombe.
- Defined new roles for calcineurin in regulating cellular processes.
- Revealed functional interactions with Pmk1 MAP kinase and PI signaling.
- Demonstrated calcineurin's involvement in membrane traffic and cytokinesis via Rab/Ypt GTPases and Type II myosin.
Conclusions:
- Fission yeast genetic studies are valuable for uncovering conserved signal transduction mechanisms.
- Calcineurin plays diverse roles in cellular regulation, including signaling, membrane dynamics, and cell division.