Involvement of calcineurin in the signal transduction of PBAN in the silkworm, Bombyx mori (Lepidoptera)

In several moth species sex pheromone production in the pheromone gland is regulated by a neurohormone, pheromone biosynthesis activating neuropeptide (PBAN). In Bombyx mori it is suggested that PBAN, after binding to the cel l-surface receptor, primarily activates a plasma membrane receptor-activate d Ca2+ channel to increase cytosolic levels of Ca2+, and Ca2+/calmodulin co mplex directly or indirectly activates a phosphoprotein phosphatase, which in turn elicits activation of acyl CoA reductase (the key enzyme under PBAN control) through dephosphorylation, resulting in pheromone (bombykol) prod uction. The effect of cyclosporin A (CsA) and FK 506, specific inhibitors o f calcineurin (phosphoprotein phosphatase 2B) was studied on the sex pherom one production, in B. mori. The in vitro experiments showed that both chemi cals exerted a dose-dependent inhibitory action when they were co-incubated with TKYFSPRL amide (Hez-PBAN fragment peptide). Practically, no differenc e was detected between the two chemicals in the tested doses (0.025-1250 mu M). When effects of CsA or FK 506 were studied on cell-free production of bombykol by using microsomal fraction no inhibition was detected. Since mic rosomal fraction contains the acyl CoA synthetase, the rate-limiting acyl C oA reductase and the precursor, bombykol is produced if supplied with CoA, ATP and NADPH. Thus, the inhibitory action of CsA and FK506 under in vitro conditions should occur before the step of acyl group reduction and the eff ect is likely to be attributable to the inhibition of calcineurin in the si gnal transduction cascade mechanism of PBAN, in B. mori. The existence of c alcineurin in the pheromone gland by using Western blot analysis is also de monstrated. (C) 1999 Elsevier Science Inc. All rights reserved.