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Teresa Duda, Alexandre Pertzev, Rameshwar K. Sharma; Signaling Helix-dependent And -independent Modulation Of Photoreceptor Guanylate Cyclase ROS-GC1 By GCAPs. Invest. Ophthalmol. Vis. Sci. 2012;53(14):754. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
To explain on structural basis the principles of Ca2+-modulated ROS-GC1 phototransduction process.
Gene deletion analysis, living cell fluorescence, co-immunoprecipitation and molecular modeling.
The coiled coil signaling helix domain has been perceived critical for the signaling integrity of all receptor membrane guanylate cyclases. The puzzle is whether it is also critical for photoreceptor ROS-GC1 modulation. The study demonstrates that the GCAP components of ROS-GC1 transduction system, GCAP1 and GCAP2, sense and transmit signals in divergent modes. The target domains of these GCAPs reside on the opposite sides of the core catalytic domain of ROS-GC1. In vivo analyses utilizing in situ living cells fluorescence show that the signaling helix of ROS-GC1 is not required for GCAPs binding to ROS-GC1. Enzymatic analyses of various deletion mutants demonstrate that GCAP2 signals activation of ROS-GC1 in the absence of the signaling helix, thus the helix is not involved in transmitting the GCAP2 signal. The helix, however, is necessary for transmitting the GCAP1 signal to the catalytic domain. Analysis of the signaling helix individual heptads indicates that they differentially influence the basal and GCAP1-stimulated activity of ROS-GC1.
GCAP1 and GCAP2 modulate Ca2+-signaling of ROS-GC1 in different fashions. The GCAP1 pathway migrates through the coiled-coil signaling helix domain to activate the catalytic site of ROS-GC1 but the helix has no role for GCAP2-modulated signaling.
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