Abstract
Retinal rods signal the activation of a single receptor molecule by a photon1. To ensure efficient photon capture, rods maintain about 109 copies of rhodopsin densely packed into membranous disks2. But a high packing density of rhodopsin may impede other steps in phototransduction that take place on the disk membrane3, by restricting the lateral movement of, and hence the rate of encounters between, the molecules involved4,5,6. Although it has been suggested that lateral diffusion of proteins on the membrane sets the rate of onset of the photoresponse7, it was later argued that the subsequent processing of the complexes was the main determinant of this rate8,9. The effects of protein density on response shut-off have not been reported. Here we show that a roughly 50% reduction in protein crowding achieved by the hemizygous knockout of rhodopsin in transgenic mice accelerates the rising phases and recoveries of flash responses by about 1.7-fold in vivo. Thus, in rods the rates of both response onset and recovery are set by the diffusional encounter frequency between proteins on the disk membrane.
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Acknowledgements
We thank P. Farabella, M. McClellan and M. Maude for technical assistance; R. Lefkowitz, A. Dizhoor, W. Smith, R. Lee, M. Simon, E. Makino and V. Arshavsky for antibodies; and E. Pugh Jr, D. Baylor and V. Arshavsky for comments on the manuscript. This work was supported by the E. Mathilda Ziegler Foundation (C.L.M.), Milton Fund (C.L.M.), the NIH (P.D.C., J.L., R.E.A.), Lion's of Massachusetts (C.L.M., J.L.), Fight for Sight (J.L.), Research to Prevent Blindness (C.L.M., J.L., R.E.A.), Foundation Fighting Blindness (J.L., R.E.A.), and the US Civilian Research and Development Foundation (V.I.G.).
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Calvert, P., Govardovskii, V., Krasnoperova, N. et al. Membrane protein diffusion sets the speed of rod phototransduction. Nature 411, 90–94 (2001). https://doi.org/10.1038/35075083
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DOI: https://doi.org/10.1038/35075083
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