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

摘要

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(q)alpha activation, while single-photon responses (quantum bumps) arise from synchronous activation of several G(q)alpha molecules. We have recently shown that most of the spontaneous single G(q)alpha activations do not produce dark bumps, because of a critical phospholipase C beta (PLC beta) activity level required for bump generation. Surpassing the threshold of channel activation depends on both PLC beta 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 PLC beta catalytic activity and the cellular [Ca2+] required for excitation. Combination of IP3R knockdown with reduced PLC beta catalytic activity resulted in highly suppressed light responses that were partially rescued by cellular Ca2+ elevation, showing a functional cooperation between IP3R and PLC beta 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 PLC beta and IP3R found here may represent a common feature of the inositol-lipid signaling.