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Y. Fu, V. Kefalov, Z. Wang, S. V. Shulga-Morskoy, J. Lem, K.-W. Yau; Gbeta.gama Subunits Are Required for the Normal Termination of Rod Photoresponse. Invest. Ophthalmol. Vis. Sci. 2007;48(13):4652.
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Retinal rods and cones have homologous but distinct heterotrimeric G proteins (transducins). Rod transducin-α (Gαt1), but not cone transducin-α (Gαt2), undergoes light-dependent translocation. We studied this difference and the importance of subunit composition of transducin in mediating light responses.
We expressed human Gαt2 (GNAT2+) in mouse rods on a Gαt1 null (gnat1-/-) or heterozygous-knockout (gnat1+/-) background. The properties of Gαt2 in mouse rods were evaluated by analyzing the interactions of transgenic Gαt2 with endogenous rhodopsin and Gß1γ1, the light-dependent translocation of Gαt2 and Gß1γ1, and the light-response properties of the GNAT2+gnat1+/- and GNAT2+gnat1-/- rods.
Gαt2 was able to substitute for Gαt1 in coupling rhodopsin to the effector (cGMP-phosphodiesterase), but with low efficiency. Transgenic Gαt2 showed light-dependent translocation in GNAT2+gnat1-/- rods, suggesting that the cellular environment rather than the properties of Gαt2 dictate translocation. Unlike in wild-type rods, Gß1γ1 in GNAT2+gnat1-/- rods failed to return to the rod outer segment (ROS) upon dark-adaptation due to their low affinity for Gαt2. Most interestingly, the decline of the light response of GNAT2+gnat1-/- rods was much prolonged. In GNAT2+gnat1-/- mice born and raised in constant darkness, most Gß1γ1 were located in the ROS, and the decline of the light response became almost normal.
Gßγ subunits are required for the normal termination of rod photoresponse.
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