Dstac Regulates Excitation-Contraction Coupling in Drosophila Body Wall Muscles

Abstract

Stac3 regulates excitation-contraction coupling (EC coupling) in vertebrate skeletal muscles by regulating the L-type voltage-gated calcium channel (Ca v channel). Recently a stac -like gene, Dstac , was identified in Drosophila and found to be expressed by both a subset of neurons and muscles. Here, we show that Dstac and Dmca1D, the Drosophila L-type Ca v channel, are necessary for normal locomotion by larvae. Immunolabeling with specific antibodies against Dstac and Dmca1D found that Dstac and Dmca1D are expressed by larval body-wall muscles. Furthermore, Ca 2+ imaging of muscles of Dstac and Dmca1D deficient larvae found that Dstac and Dmca1D are required for excitation-contraction coupling. Finally, Dstac appears to be required for normal expression levels of Dmca1D in body-wall muscles. These results suggest that Dstac regulates Dmca1D during EC coupling and thus muscle contraction.

Comparison of excitation–contraction coupling between Drosophila and vertebrate muscle

“…Reduction in Ca 2+ release from the SR was induced by genetic knockdown of RyR expression and caused a substantial reduction in muscle force production at each stimulation frequency in the force-frequency curve. This is consistent with previous work, which has shown that RyR is widely expressed in larval muscle and that both pharmacological inhibition and partial loss-of-function mutation caused impairments in locomotion by larvae (Hsu et al 2020). Likewise, it is akin to impairments in Ca 2+ release in vertebrate muscle; with reduced Ca 2+ release, less cytosolic Ca 2+ is present to generate force (Bers, 2002;Calderon et al 2014).…”

“…This is consistent with previous work showing that a dominant heat‐inducible mutation of SERCA paralyses larvae, illustrating temperature sensitivity of contraction‐related proteins (Hsu et al . 2020). The relationship between temperature and contractile kinetics has been extensively examined in vertebrate skeletal and cardiac muscle and has shown great variability depending on numerous factors including muscle type, fibre‐type and age.…”

“…This process has been studied across the animal phyla, though perhaps most extensively in vertebrates. In vertebrate skeletal muscle, ECC is reliant upon voltage-dependent Ca 2+ release and is mediated by an allosteric interaction between the voltage sensing L-type Ca v channel, dihydropyridine receptor and the Ca 2+ release channel ryanodine receptor (RyR) (Hsu et al 2020). Conversely, vertebrate cardiac and smooth muscle ECC requires an influx of Ca 2+ through Ca v channels, which initiates Ca 2+ -induced Ca 2+ release (CICR) from internal Ca 2+ stores.…”

“…Excitation-contraction coupling (ECC) describes the physiological process by which an electrical stimulus is converted to a mechanical response. Briefly, the change in muscle fibre membrane voltage elicits a rise in cytosolic calcium (Ca 2+ ) which subsequently induces contraction (Hsu et al 2020). This process has been studied across the animal phyla, though perhaps most extensively in vertebrates.…”

Stac protein regulates release of neuropeptides

“…The muscle expression of Dstac suggests that Dstac might regulate EC coupling in larval body wall muscles of Drosophila just as Stac3 in vertebrate skeletal muscles. In fact, selective knockdown of either Dmca1D or Dstac in muscles decreased activation-mediated Ca 2+ transients in muscles, suggesting that Dstac regulates EC coupling in Drosophila larval muscles (67). In some invertebrate muscles, including those of Drosophila, EC coupling is thought to involve CICR (68)(69)(70)(71)(72).…”