Functional Cooperation between the IP₃ Receptor and Phospholipase C Secures the High Sensitivity to Light of Drosophila Photoreceptors In Vivo

Abstract

Drosophila phototransduction is a model system for the ubiquitous phosphoinositide signaling. In complete darkness, spontaneous unitary current events (dark bumps) are produced by spontaneous single G_qα activation, while single-photon responses (quantum bumps) arise from synchronous activation of several G_qα molecules. We have recently shown that most of the spontaneous single G_qα activations do not produce dark bumps, because of a critical phospholipase Cβ (PLCβ) activity level required for bump generation. Surpassing the threshold of channel activation depends on both PLCβ activity and cellular [Ca²⁺], which participates in light excitation via a still unclear mechanism. We show here that in IP₃ receptor (IP₃R)-deficient photoreceptors, both light-activated Ca²⁺ release from internal stores and light sensitivity were strongly attenuated. This was further verified by Ca²⁺ store depletion, linking Ca²⁺ release to light excitation. In IP₃R-deficient photoreceptors, dark bumps were virtually absent and the quantum-bump rate was reduced, indicating that Ca²⁺ release from internal stores is necessary to reach the critical level of PLCβ catalytic activity and the cellular [Ca²⁺] required for excitation. Combination of IP₃R knockdown with reduced PLCβ catalytic activity resulted in highly suppressed light responses that were partially rescued by cellular Ca²⁺ elevation, showing a functional cooperation between IP₃R and PLCβ via released Ca²⁺. These findings suggest that in contrast to the current dogma that Ca²⁺ release via IP₃R does not participate in light excitation, we show that released Ca²⁺ plays a critical role in light excitation. The positive feedback between PLCβ and IP₃R found here may represent a common feature of the inositol-lipid signaling.