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000282562 1001_ $$00009-0002-5649-4364$$aSpreen, Anika$$b0
000282562 245__ $$aOptogenetic silencing by combining a rhodopsin cyclase with an engineered cGMP-gated potassium channel.
000282562 260__ $$aWashington, DC [u.a.]$$bAssoc.$$c2025
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000282562 520__ $$aSince the advent of optogenetics, great progress has been made in developing tools to modulate and detect cellular activity using light. We present a two-component optogenetic silencing tool, RoCK (rhodopsin cyclase/K+ channel), which pairs the rhodopsin-guanylyl cyclase CaRhGC with customized SthK K+ channels that are engineered to open selectively upon guanosine 3',5'-monophosphate (cGMP) binding. By enhancing the cGMP sensitivity and open probability of SthK mutants, we obtained four channel variants suited for different levels of cGMP concentration. CaRhGC's membrane-bound nature enables localized cGMP production, and the lack of dark activity reduces the risk for off-target effects. Optimized RoCK effectively modulated cellular activity in mouse hippocampal neurons, in acute hippocampal slices, and in rabbit cardiomyocytes. In zebrafish, RoCK silenced motor neurons in vivo, suppressing the characteristic coiling behavior of embryos, thus highlighting its potential for behavioral studies. In summary, RoCK expands our optogenetic toolkit threefold for fast cGMP production, fast cGMP sensing, and K+-based cell silencing.
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000282562 650_7 $$0H2D2X058MU$$2NLM Chemicals$$aCyclic GMP
000282562 650_7 $$09009-81-8$$2NLM Chemicals$$aRhodopsin
000282562 650_7 $$0EC 4.6.1.2$$2NLM Chemicals$$aGuanylate Cyclase
000282562 650_7 $$2NLM Chemicals$$aPotassium Channels
000282562 650_2 $$2MeSH$$aOptogenetics: methods
000282562 650_2 $$2MeSH$$aAnimals
000282562 650_2 $$2MeSH$$aCyclic GMP: metabolism
000282562 650_2 $$2MeSH$$aMice
000282562 650_2 $$2MeSH$$aRhodopsin: metabolism
000282562 650_2 $$2MeSH$$aRhodopsin: genetics
000282562 650_2 $$2MeSH$$aHumans
000282562 650_2 $$2MeSH$$aHippocampus: metabolism
000282562 650_2 $$2MeSH$$aHippocampus: cytology
000282562 650_2 $$2MeSH$$aGuanylate Cyclase: metabolism
000282562 650_2 $$2MeSH$$aGuanylate Cyclase: genetics
000282562 650_2 $$2MeSH$$aZebrafish
000282562 650_2 $$2MeSH$$aPotassium Channels: metabolism
000282562 650_2 $$2MeSH$$aPotassium Channels: genetics
000282562 650_2 $$2MeSH$$aProtein Engineering
000282562 650_2 $$2MeSH$$aMyocytes, Cardiac: metabolism
000282562 650_2 $$2MeSH$$aNeurons: metabolism
000282562 650_2 $$2MeSH$$aHEK293 Cells
000282562 7001_ $$00000-0003-1534-831X$$aSadanandan, Nidish Ponath$$b1
000282562 7001_ $$00000-0001-9760-6292$$aSchneider, Martin Winfried$$b2
000282562 7001_ $$00000-0003-3428-5860$$aKuehn, Enrico$$b3
000282562 7001_ $$00009-0009-8156-2155$$aLeemisa, Andries Napo$$b4
000282562 7001_ $$00000-0002-1777-2088$$aDe Zio, Roberta$$b5
000282562 7001_ $$00009-0004-6794-1267$$aMeyer, Niklas$$b6
000282562 7001_ $$00009-0006-4364-7914$$aBusse, Wayne$$b7
000282562 7001_ $$00009-0002-3198-3137$$aErlinghagen, Bela$$b8
000282562 7001_ $$aAdenauer, Lea$$b9
000282562 7001_ $$0P:(DE-2719)9000241$$aOpitz, Thoralf$$b10
000282562 7001_ $$aBönigk, Wolfgang$$b11
000282562 7001_ $$00000-0001-7913-5597$$aSchiewer, Enrico$$b12
000282562 7001_ $$00009-0003-1844-5331$$aHeer, Jonas$$b13
000282562 7001_ $$0P:(DE-2719)2810725$$aSchmitz, Dietmar$$b14
000282562 7001_ $$00000-0001-7368-5539$$aVierock, Johannes$$b15
000282562 7001_ $$0P:(DE-2719)2000044$$aBeck, Heinz$$b16
000282562 7001_ $$00000-0003-3589-6452$$aHegemann, Peter$$b17
000282562 7001_ $$00000-0002-7268-0469$$aBaier, Herwig$$b18
000282562 7001_ $$00000-0002-5873-9436$$aSchneider-Warme, Franziska$$b19
000282562 7001_ $$00000-0003-3067-7496$$aSierra, Yinth Andrea Bernal$$b20
000282562 7001_ $$00009-0003-5872-4845$$aSeifert, Reinhard$$b21
000282562 773__ $$0PERI:(DE-600)2810933-8$$a10.1126/sciadv.adx1195$$gVol. 11, no. 48, p. eadx1195$$n48$$peadx1195$$tScience advances$$v11$$x2375-2548$$y2025
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