Abstract
Appropriate termination of the phototransduction cascade is critical for photoreceptors to achieve high temporal resolution and to prevent excessive Ca(2+)-induced cell toxicity. Using a genetic screen to identify defective photoresponse mutants in Drosophila, we isolated and identified a novel Gα(q) mutant allele, which has defects in both activation and deactivation. We revealed that G(q) modulates the termination of the light response and that metarhodopsin/G(q) interaction affects subsequent arrestin-rhodopsin (Arr2-Rh1) binding, which mediates the deactivation of metarhodopsin. We further showed that the Gα(q) mutant undergoes light-dependent retinal degeneration, which is due to the slow accumulation of stable Arr2-Rh1 complexes. Our study revealed the roles of G(q) in mediating photoresponse termination and in preventing retinal degeneration. This pathway may represent a general rapid feedback regulation of G protein-coupled receptor signaling.
Highlights
Appropriate termination of photoresponse is critical for photoreceptors to achieve high temporal resolution and to prevent excessive Ca2ϩ-induced cell toxicity
We revealed that Gq modulates the termination of the light response and that metarhodopsin/Gq interaction affects subsequent arrestin-rhodopsin (Arr2-Rh1) binding, which mediates the deactivation of metarhodopsin
Our work isolated and identified a novel G␣q mutant allele and demonstrated that metarhodopsin/Gq interaction affects subsequent Arr2-Rh1 binding, which might mediate the deactivation of metarhodopsin
Summary
Appropriate termination of photoresponse is critical for photoreceptors to achieve high temporal resolution and to prevent excessive Ca2ϩ-induced cell toxicity. We revealed that Gq modulates the termination of the light response and that metarhodopsin/Gq interaction affects subsequent arrestin-rhodopsin (Arr2-Rh1) binding, which mediates the deactivation of metarhodopsin. Our study revealed the roles of Gq in mediating photoresponse termination and in preventing retinal degeneration. This pathway may represent a general rapid feedback regulation of G protein-coupled receptor signaling. The activation of PLC leads to transient receptor potential and transient receptor potential-like channels opening and extracellular Ca2ϩ influx [5,6,7,8] It is critical for each step of the phototransduction cascade to be terminated appropriately, which is essential for the high temporal resolution of fly vision [9, 10]. This pathway represents a general rapid feedback regulation in GPCR signaling
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