Optical Control of an Ion Channel Gate

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2013 Dec 4

PMID 24297890

Citations 23

Authors

Damien Lemoine

Chloe Habermacher

Adeline Martz

Pierre-Francois Mery

Nathalie Bouquier

Fanny Diverchy

Antoine Taly

Francois Rassendren

Alexandre Specht

Thomas Grutter

Affiliations

Soon will be listed here.

Abstract

The powerful optogenetic pharmacology method allows the optical control of neuronal activity by photoswitchable ligands tethered to channels and receptors. However, this approach is technically demanding, as it requires the design of pharmacologically active ligands. The development of versatile technologies therefore represents a challenging issue. Here, we present optogating, a method in which the gating machinery of an ATP-activated P2X channel was reprogrammed to respond to light. We found that channels covalently modified by azobenzene-containing reagents at the transmembrane segments could be reversibly turned on and off by light, without the need of ATP, thus revealing an agonist-independent, light-induced gating mechanism. We demonstrate photocontrol of neuronal activity by a light-gated, ATP-insensitive P2X receptor, providing an original tool devoid of endogenous sensitivity to delineate P2X signaling in normal and pathological states. These findings open new avenues to specifically activate other ion channels independently of their natural stimulus.

Citing Articles

Optical control of PIEZO1 channels.

Peralta F, Balcon M, Martz A, Biljali D, Cevoli F, Arnould B Nat Commun. 2023; 14(1):1269.

PMID: 36882406 PMC: 9992513. DOI: 10.1038/s41467-023-36931-0.

Photopharmacology of Ion Channels through the Light of the Computational Microscope.

Nin-Hill A, Mueller N, Molteni C, Rovira C, Alfonso-Prieto M Int J Mol Sci. 2021; 22(21).

PMID: 34769504 PMC: 8584574. DOI: 10.3390/ijms222112072.

Optical control of purinergic signaling.

Wang T, Ulrich H, Semyanov A, Illes P, Tang Y Purinergic Signal. 2021; 17(3):385-392.

PMID: 34156578 PMC: 8410941. DOI: 10.1007/s11302-021-09799-2.

A fine-tuned azobenzene for enhanced photopharmacology in vivo.

Gutzeit V, Acosta-Ruiz A, Munguba H, Hafner S, Landra-Willm A, Mathes B Cell Chem Biol. 2021; 28(11):1648-1663.e16.

PMID: 33735619 PMC: 8435545. DOI: 10.1016/j.chembiol.2021.02.020.

Reversible Photocontrolled Nanopore Assembly.

Mutter N, Volaric J, Szymanski W, Feringa B, Maglia G J Am Chem Soc. 2019; 141(36):14356-14363.

PMID: 31469268 PMC: 6743218. DOI: 10.1021/jacs.9b06998.

References

Szymanski W, Beierle J, Kistemaker H, Velema W, Feringa B . Reversible photocontrol of biological systems by the incorporation of molecular photoswitches. Chem Rev. 2013; 113(8):6114-78. DOI: 10.1021/cr300179f. View

Bo X, Jiang L, Wilson H, Kim M, Burnstock G, Surprenant A . Pharmacological and biophysical properties of the human P2X5 receptor. Mol Pharmacol. 2003; 63(6):1407-16. DOI: 10.1124/mol.63.6.1407. View

Browne L, Cao L, Broomhead H, Bragg L, Wilkinson W, North R . P2X receptor channels show threefold symmetry in ionic charge selectivity and unitary conductance. Nat Neurosci. 2010; 14(1):17-8. PMC: 3012030. DOI: 10.1038/nn.2705. View

Gorostiza P, Isacoff E . Optical switches for remote and noninvasive control of cell signaling. Science. 2008; 322(5900):395-9. PMC: 7592022. DOI: 10.1126/science.1166022. View

Deisseroth K . Optogenetics. Nat Methods. 2010; 8(1):26-9. PMC: 6814250. DOI: 10.1038/nmeth.f.324. View

Jiang L, Rassendren F, Spelta V, Surprenant A, North R . Amino acid residues involved in gating identified in the first membrane-spanning domain of the rat P2X(2) receptor. J Biol Chem. 2001; 276(18):14902-8. DOI: 10.1074/jbc.M011327200. View

Jiang R, Taly A, Lemoine D, Martz A, Cunrath O, Grutter T . Tightening of the ATP-binding sites induces the opening of P2X receptor channels. EMBO J. 2012; 31(9):2134-43. PMC: 3343472. DOI: 10.1038/emboj.2012.75. View

Wyart C, Del Bene F, Warp E, Scott E, Trauner D, Baier H . Optogenetic dissection of a behavioural module in the vertebrate spinal cord. Nature. 2009; 461(7262):407-10. PMC: 2770190. DOI: 10.1038/nature08323. View

Volgraf M, Gorostiza P, Numano R, Kramer R, Isacoff E, Trauner D . Allosteric control of an ionotropic glutamate receptor with an optical switch. Nat Chem Biol. 2006; 2(1):47-52. PMC: 1447676. DOI: 10.1038/nchembio756. View

10.

Baccam N, Alonso G, Costecalde T, Fontanaud P, Molino F, Robinson I . Dual-level afferent control of growth hormone-releasing hormone (GHRH) neurons in GHRH-green fluorescent protein transgenic mice. J Neurosci. 2007; 27(7):1631-41. PMC: 6673740. DOI: 10.1523/JNEUROSCI.2693-06.2007. View

11.

Li M, Chang T, Silberberg S, Swartz K . Gating the pore of P2X receptor channels. Nat Neurosci. 2008; 11(8):883-7. PMC: 2629452. DOI: 10.1038/nn.2151. View

12.

Adesnik H, Scanziani M . Lateral competition for cortical space by layer-specific horizontal circuits. Nature. 2010; 464(7292):1155-60. PMC: 2908490. DOI: 10.1038/nature08935. View

13.

Szobota S, Gorostiza P, Del Bene F, Wyart C, Fortin D, Kolstad K . Remote control of neuronal activity with a light-gated glutamate receptor. Neuron. 2007; 54(4):535-45. DOI: 10.1016/j.neuron.2007.05.010. View

14.

Banghart M, Borges K, Isacoff E, Trauner D, Kramer R . Light-activated ion channels for remote control of neuronal firing. Nat Neurosci. 2004; 7(12):1381-6. PMC: 1447674. DOI: 10.1038/nn1356. View

15.

Hattori M, Gouaux E . Molecular mechanism of ATP binding and ion channel activation in P2X receptors. Nature. 2012; 485(7397):207-12. PMC: 3391165. DOI: 10.1038/nature11010. View

16.

White N, Burnstock G . P2 receptors and cancer. Trends Pharmacol Sci. 2006; 27(4):211-7. DOI: 10.1016/j.tips.2006.02.004. View

17.

Lomize M, Lomize A, Pogozheva I, Mosberg H . OPM: orientations of proteins in membranes database. Bioinformatics. 2006; 22(5):623-5. DOI: 10.1093/bioinformatics/btk023. View

18.

Browne L, Compan V, Bragg L, North R . P2X7 receptor channels allow direct permeation of nanometer-sized dyes. J Neurosci. 2013; 33(8):3557-66. PMC: 6619550. DOI: 10.1523/JNEUROSCI.2235-12.2013. View

19.

Yan Z, Li S, Liang Z, Tomic M, Stojilkovic S . The P2X7 receptor channel pore dilates under physiological ion conditions. J Gen Physiol. 2008; 132(5):563-73. PMC: 2571973. DOI: 10.1085/jgp.200810059. View

20.

Kaczmarek-Hajek K, Lorinczi E, Hausmann R, Nicke A . Molecular and functional properties of P2X receptors--recent progress and persisting challenges. Purinergic Signal. 2012; 8(3):375-417. PMC: 3360091. DOI: 10.1007/s11302-012-9314-7. View