Calcineurin is part of a negative feedback loop in the InsP3/Ca signalling pathway in blowfly salivary glands |
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Authors: | Kristoffer Heindorff Otto Baumann |
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Affiliation: | Institute of Biochemistry and Biology, Department of Animal Physiology, University of Potsdam, Karl-Liebknecht-Str. 24/25, 14476 Potsdam, Germany |
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Abstract: | The ubiquitous InsP3/Ca2+ signalling pathway is modulated by diverse mechanisms, i.e. feedback of Ca2+ and interactions with other signalling pathways. In the salivary glands of the blowfly Calliphora vicina, the hormone serotonin (5-HT) causes a parallel rise in intracellular [Ca2+] and [cAMP] via two types of 5-HT receptors. We have shown recently that cAMP/protein kinase A (PKA) sensitizes InsP3-induced Ca2+ release. We have now identified the protein phosphatase that counteracts the effect of PKA on 5-HT-induced InsP3/Ca2+ signalling. We demonstrate that (1) tautomycin and okadaic acid, inhibitors of protein phosphatases PP1 and PP2A, have no effect on 5-HT-induced Ca2+ signals; (2) cyclosporin A and FK506, inhibitors of Ca2+/calmodulin-activated protein phosphatase calcineurin, cause an increase in the frequency of 5-HT-induced Ca2+ oscillations; (3) the sensitizing effect of cyclosporin A on 5-HT-induced Ca2+ responses does not involve Ca2+ entry into the cells; (4) cyclosporin A increases InsP3-dependent Ca2+ release; (5) inhibition of PKA abolishes the effect of cyclosporin A on the 5-HT-induced Ca2+ responses, indicating that PKA and calcineurin act antagonistically on the InsP3/Ca2+ signalling pathway. These findings suggest that calcineurin provides a negative feedback on InsP3/Ca2+ signalling in blowfly salivary glands, counteracting the effect of PKA and desensitizing the signalling cascade at higher 5-HT concentrations. |
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Keywords: | Calcineurin Ca2+ Ca2+ oscillations cAMP Protein kinase A Intracellular signalling Salivary gland Blowfly Insect |
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