TY  - JOUR
A1  - Heindorff, Kristoffer
A1  - Baumann, Otto
T1  - Calcineurin is part of a negative feedback loop in the InsP(3)/Ca2+ signalling pathway in blowfly salivary glands
JF  - Cell calcium
N2  - The ubiquitous InsP(3)/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 InsP(3)-induced Ca2+ release. We have now identified the protein phosphatase that counteracts the effect of PKA on 5-HT-induced InsP(3)/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 InsP(3)-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 InsP(3)/Ca2+ signalling pathway. These findings suggest that calcineurin provides a negative feedback on InsP(3)/Ca2+ signalling in blowfly salivary glands, counteracting the effect of PKA and desensitizing the signalling cascade at higher 5-HT concentrations. (C) 2014 Elsevier Ltd. All rights reserved.
KW  - Calcineurin
KW  - Ca2+
KW  - Ca2+ oscillations
KW  - cAMP
KW  - Protein kinase A
KW  - Intracellular signalling
KW  - Salivary gland
KW  - Blowfly
KW  - Insect
Y1  - 2014
U6  - https://doi.org/10.1016/j.ceca.2014.07.009
SN  - 0143-4160
SN  - 1532-1991
VL  - 56
IS  - 3
SP  - 215
EP  - 224
PB  - Churchill Livingstone
CY  - Edinburgh
ER  - 
TY  - JOUR
A1  - Heindorff, Kristoffer
A1  - Blenau, Wolfgang
A1  - Walz, Bernd
A1  - Baumann, Otto
T1  - Characterization of a Ca2+/calmodulin-dependent AC1 adenylyl cyclase in a non-neuronal tissue, the blowfly salivary gland
JF  - Cell calcium
N2  - Crosstalk between intracellular signalling pathways is a functionally important and widespread phenomenon in cell physiology across phyla. In the salivary gland of the blowfly, serotonin induces fluid secretion via parallel activation of both the InsP(3)/Ca2+ and the cAMP/PKA signalling pathways, which interact on multiple levels. We have determined the molecular identity of a link between both pathways that mediates a Ca2+-dependent rise of intracellular cAMP. Whereas hydrolysis of cAMP via phosphodiesterases is largely independent of Ca2+, cAMP synthesis by adenylyl cyclases (AC) is potentiated in a Ca2+/calmodulin (Ca2+/CaM)-dependent manner. The existence of a Ca2+/CaM-dependent AC is supported by physiological data and a molecular approach. We have cloned Cv rutabaga cDNA, encoding the first blowfly AC, and confirmed its expression in the salivary gland via reverse transcription followed by polymerase chain reaction. The putative gene product of Cv rutabaga is a Ca2+/CaM-dependent type I AC and shows highest homology to Rutabaga from Drosophila. Thus, a Ca2+/CaM-dependent AC serves as a link between the InsP(3)/Ca2+ and the cAMP/PKA signalling pathways in the salivary gland of the blowfly and might be important for the amplification and optimization of the secretory response.
KW  - Adenylyl cyclase
KW  - Phosphodiesterase
KW  - Crosstalk
KW  - Ca2+
KW  - cAMP
KW  - Intracellular signalling
KW  - Salivary gland
KW  - Calliphora vicina
KW  - Rutabaga
Y1  - 2012
U6  - https://doi.org/10.1016/j.ceca.2012.04.016
SN  - 0143-4160
VL  - 52
IS  - 2
SP  - 103
EP  - 112
PB  - Churchill Livingstone
CY  - Edinburgh
ER  -