Knock down of Calcineurin-B2, a calcium binding regulatory subunit of Calcineurin, gives rise to hypercontraction myopathy in indirect flight muscles of Drosophila through dysregulation of calcium homeostasis

Abstract

Abstract/SummaryMuscle is a calcium responsive tissue and requires calcium for initiation of muscle contraction. Calcium concentration in muscle is tightly regulated by calcium binding proteins. Calcineurin-B2 (canB2), a calcium binding, regulatory subunit of calcineurin, is the isoform maximally expressed in the indirect flight muscles (IFMs) of Drosophila. The developmental and functional roles of CanB2 particularly in the maintenance of calcium homeostasis are not understood. In this study, we show that the loss of canB2 causes hypercontraction of IFMs. Genetic interaction studies with hypercontraction mutants suggest a synergistic interaction between Calcineurin-B2 and structural protein Troponin-T. Similarly, interaction studies with dSERCA mutant reveal that Calcineurin-B2 is important for regulating calcium homeostasis in muscles. In vivo calcium imaging showed that Calcineurin-B2 deficiency leads to arrhythmicity in the calcium oscillations. We show that Calcineurin-B2 knockdown causes deregulation of calcium homeostasis, which results in unregulated acto-myosin interaction. However, overexpression of Calcineurin-A, which inhibits calcium oscillations, had no effect on myofibrillogenesis suggesting that calcium activation is dispensable for myofibrillar assembly. Our findings contribute to the understanding of muscle physiology in normal as well as pathophysiological conditions.