G-protein deactivation is rate-limiting for shut-off of the phototransduction cascade

ABSTRACT Photoreceptors detect light through a seven-helix receptor (rhodopsin) and heterotrimeric G protein (transducin) coupled to a cyclic GMP phosphodiesterase1,2. Similar pathways are

used to amplify responses to hormones, taste and smell3,4,5. The amplification of phototransduction is reduced by a fall in cytoplasmic Ca2+ (refs 6, 7, 8, 9, 10), but it is not known how

the deactivation of rhodopsin and transducin influence this response and hence the extent and duration of phosphodiesterase activity11,12,13,14. Here we investigate this by recording the

electrical response to flashes of light in truncated rod photoreceptors10. By removing ATP to block the deactivation of rhodopsin by phosphorylation15, we show that this reaction limits the

amplitude of the response and begins within 3.2 s of a flash in a solution containing 1 μM Ca2+, falling to 0.9 s in a zero-Ca2+ solution. In contrast, the activation and amplitude of the

response were unaffected when transducin deactivation by GTP hydrolysis was blocked by replacing GTP with its non-hydrolysable analogue GTP-γS11, demonstrating that there is little GTP

hydrolysis occurring over the period in which photoexcited rhodopsin is quenched. The rapid deactivation of rhodopsin is therefore a Ca2+-sensitive step controlling the amplitude of the

light response, whereas transducin deactivation is slower and controls recovery. Access through your institution Buy or subscribe This is a preview of subscription content, access via your

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ROD PHOTORECEPTORS Article Open access 26 April 2021 ULTRAFAST STRUCTURAL CHANGES DIRECT THE FIRST MOLECULAR EVENTS OF VISION Article Open access 22 March 2023 ACTIVE STATE STRUCTURES OF A

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apparent affinity of transducin for GTP. _Invest. Ophthalmol. Vis. Sci._ 38, S614 (1997). Google Scholar  Download references ACKNOWLEDGEMENTS We thank C. Raeburn of the LMB Instrumentation

Workshop for assistance. This work was supported by the HFSP. M.S.S. held a scholarship of the University of Cambridge M.B, Ph.D. Programme. AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * MRC

Laboratory of Molecular Biology, Hills Road, CB2 2QH, Cambridge, UK Mandeep S. Sagoo * MRC Laboratory of Molecular Biology, Hills Road, CB2 2QH, Cambridge, UK Leon Lagnado Authors * Mandeep

S. Sagoo View author publications You can also search for this author inPubMed Google Scholar * Leon Lagnado View author publications You can also search for this author inPubMed Google

Scholar CORRESPONDING AUTHOR Correspondence to Leon Lagnado. RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Sagoo, M., Lagnado, L. G-protein

deactivation is rate-limiting for shut-off of the phototransduction cascade. _Nature_ 389, 392–395 (1997). https://doi.org/10.1038/38750 Download citation * Received: 01 May 1997 * Accepted:

07 July 1997 * Issue Date: 25 September 1997 * DOI: https://doi.org/10.1038/38750 SHARE THIS ARTICLE Anyone you share the following link with will be able to read this content: Get

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