title: 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 Gqα activation, while single-photon responses (quantum bumps) arise from synchronous activation of several Gqα molecules. We have recently shown that most of the spontaneous single Gqα 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 [Ca(2+)], which participates in light excitation via a still unclear mechanism. We show here that in IP3 receptor (IP3R)-deficient photoreceptors, both light-activated Ca(2+) release from internal stores and light sensitivity were strongly attenuated. This was further verified by Ca(2+) store depletion, linking Ca(2+) release to light excitation. In IP3R-deficient photoreceptors, dark bumps were virtually absent and the quantum-bump rate was reduced, indicating that Ca(2+) release from internal stores is necessary to reach the critical level of PLCβ catalytic activity and the cellular [Ca(2+)] required for excitation. Combination of IP3R knockdown with reduced PLCβ catalytic activity resulted in highly suppressed light responses that were partially rescued by cellular Ca(2+) elevation, showing a functional cooperation between IP3R and PLCβ via released Ca(2+). These findings suggest that in contrast to the current dogma that Ca(2+) release via IP3R does not participate in light excitation, we show that released Ca(2+) 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.
authors: Departments of Medical Neurobiology, the Institute of Medical Research Israel-Canada, and the Edmond and Lily Safra Center for Brain Sciences, Faculty of Medicine of the Hebrew University, Jerusalem 91120, Israel.
authors: Elkana
authors: E
authors: Kohn
authors: Departments of Medical Neurobiology, the Institute of Medical Research Israel-Canada, and the Edmond and Lily Safra Center for Brain Sciences, Faculty of Medicine of the Hebrew University, Jerusalem 91120, Israel.
authors: Ben
authors: B
authors: Katz
authors: Departments of Medical Neurobiology, the Institute of Medical Research Israel-Canada, and the Edmond and Lily Safra Center for Brain Sciences, Faculty of Medicine of the Hebrew University, Jerusalem 91120, Israel.
authors: Bushra
authors: B
authors: Yasin
authors: Departments of Medical Neurobiology, the Institute of Medical Research Israel-Canada, and the Edmond and Lily Safra Center for Brain Sciences, Faculty of Medicine of the Hebrew University, Jerusalem 91120, Israel.
authors: Maximilian
authors: M
authors: Peters
authors: Departments of Medical Neurobiology, the Institute of Medical Research Israel-Canada, and the Edmond and Lily Safra Center for Brain Sciences, Faculty of Medicine of the Hebrew University, Jerusalem 91120, Israel.
authors: Elisheva
authors: E
authors: Rhodes
authors: Departments of Medical Neurobiology, the Institute of Medical Research Israel-Canada, and the Edmond and Lily Safra Center for Brain Sciences, Faculty of Medicine of the Hebrew University, Jerusalem 91120, Israel.
authors: Rachel
authors: R
authors: Zaguri
authors: Departments of Medical Neurobiology, the Institute of Medical Research Israel-Canada, and the Edmond and Lily Safra Center for Brain Sciences, Faculty of Medicine of the Hebrew University, Jerusalem 91120, Israel.
authors: Shirley
authors: S
authors: Weiss
authors: Departments of Medical Neurobiology, the Institute of Medical Research Israel-Canada, and the Edmond and Lily Safra Center for Brain Sciences, Faculty of Medicine of the Hebrew University, Jerusalem 91120, Israel baruchm@ekmd.huji.ac.il.
authors: Baruch
authors: B
authors: Minke
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D020013:Calcium Signaling / Q000502:physiology; D004330:Drosophila / Q000502:physiology*; D004596:Electroretinography; D000860:Hypoxia / Q000378:metabolism; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000235:genetics / Q000502:physiology*; D008027:Light; D008297:Male; D018408:Patch-Clamp Techniques; D054799:Phospholipase C beta / Q000502:physiology*; D017956:Photoreceptor Cells, Invertebrate / Q000502:physiology* / Q000528:radiation effects; D034622:RNA Interference
chemical_list: D053496:Inositol 1,4,5-Trisphosphate Receptors; D054799:Phospholipase C beta
keywords: Ca2+ release; Drosophila; IP3 receptor; phospholipase C; photoreceptors; phototransduction