Ca²⁺-Dependent Metarhodopsin Inactivation Mediated by Calmodulin and NINAC Myosin III

Phototransduction in flies is the fastest known G protein-coupled signaling cascade, but how this performance is achieved remains unclear. Here, we investigate the mechanism and role of rhodopsin inactivation. We determined the lifetime of activated rhodopsin (metarhodopsin = M^*) in whole-cell recordings from Drosophila photoreceptors by measuring the time window within which inactivating M^* by photoreisomerization to rhodopsin could suppress responses to prior illumination. M^* was inactivated rapidly (τ ∼20 ms) under control conditions, but ∼10-fold more slowly in Ca²⁺-free solutions. This pronounced Ca²⁺ dependence of M^* inactivation was unaffected by mutations affecting phosphorylation of rhodopsin or arrestin but was abolished in mutants of calmodulin (CaM) or the CaM-binding myosin III, NINAC. This suggests a mechanism whereby Ca²⁺ influx acting via CaM and NINAC accelerates the binding of arrestin to M^*. Our results indicate that this strategy promotes quantum efficiency, temporal resolution, and fidelity of visual signaling.