Optogenetic manipulation of Gq- and Gi/o-coupled receptor signaling in neurons and heart muscle cells

Hagio, Hanako; Koyama, Wataru; Hosaka, Shiori; Song, Aysenur Deniz; Narantsatsral, Janchiv; Matsuda, Kōji; Sugihara, Tomohiro; Shimizu, Takashi; Koyanagi, Mitsumasa; Terakita, Akihisa; Hibi, Masahiko

doi:10.1101/2022.10.25.513732

Cited by 2 publications

(2 citation statements)

References 76 publications

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“…Bistable opsins are promising for optogenetic applications because they can be activated and inactivated with specific wavelengths of light, providing high temporal precision. For instance, JSR1 has been used as an optogenetic tool in zebrafish reticulospinal V2a neurons, where activation of JSR1 lead to an increase of Ca 2+ and evoked a change in swimming behaviour [44]. The main issue with using JSR1 as an optogenetic tool is that the λ max of the active and inactive states overlap, meaning that there will be a mixture of active and inactive states upon illumination and the activity of JSR1 cannot be controlled precisely [16].…”

Section: Discussionmentioning

confidence: 99%

Active state structures of a bistable visual opsin bound to G proteins

Tejero,

Pamula,

Koyanagi

et al. 2024

Preprint

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Opsins are G protein-coupled receptors (GPCRs) that have evolved to detect light stimuli and initiate intracellular signaling cascades. Their role as signal transducers is critical to light perception across the animal kingdom. Opsins covalently bind to the chromophore 11-cis retinal, which isomerizes to the all-trans isomer upon photon absorption, causing conformational changes that result in receptor activation. Monostable opsins, responsible for vision in vertebrates, release the chromophore after activation and must bind another retinal molecule to remain functional. In contrast, bistable opsins, responsible for non-visual light perception in vertebrates and for vision in invertebrates, absorb a second photon in the active state to return the chromophore and protein to the inactive state. Structures of bistable opsins in the activated state have proven elusive, limiting our understanding of how they function as bidirectional photoswitches. Here we present active state structures of a bistable opsin, jumping spider rhodopsin isoform-1 (JSR1), in complex with its downstream signaling partners, the Gi and Gq heterotrimers. These structures elucidate key differences in the activation mechanisms between monostable and bistable opsins, offering essential insights for the rational engineering of bistable opsins into diverse optogenetic tools to control G protein signaling pathways.

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Section: Discussionmentioning

confidence: 99%

Active state structures of a bistable visual opsin bound to G proteins

Tejero,

Pamula,

Koyanagi

et al. 2024

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

“…They are therefore classified as ‘bistable’ due to the thermal stability of the PSB in both the inactive and active states. Bistable opsins are potential optogenetic switches to control G protein signaling pathways, and in vivo studies have demonstrated the capability of JSR1 as an optogenetic tool to manipulate neuronal signaling in animals (5).…”

Section: Introductionmentioning

confidence: 99%

Activating an invertebrate bistable opsin with the all-trans 6.11 retinal analogue

Rodrigues,

Tejero,

Mühle

et al. 2024

Preprint

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Animal vision depends on opsins, a category of G protein-coupled receptor (GPCR) that achieves light sensitivity by covalent attachment to retinal. Typically binding as an inverse agonist in the 11-cis form, retinal photoisomerizes to the all-trans isomer and activates the receptor, initiating downstream signaling cascades. Retinal bound to bistable opsins isomerizes back to the 11-cis state after absorption of a second photon, inactivating the receptor. Bistable opsins are essential for invertebrate vision and non-visual light perception across the animal kingdom. While crystal structures are available for bistable opsins in the inactive state, it has proven difficult to form homogeneous populations of activated bistable opsins either via illumination or reconstitution with all-trans retinal. Here we show that a non-natural retinal analogue, all-trans retinal 6.11 (ATR6.11), can be reconstituted with the invertebrate bistable opsin, Jumping Spider Rhodopsin-1 (JSR1). Biochemical activity assays demonstrate that ATR6.11 functions as an agonist of JSR1. ATR6.11 binding also enables complex formation between JSR1 and downstream signaling partners. Our findings demonstrate the utility of retinal analogues for biophysical characterization of bistable opsins, which will deepen our understanding of light perception in animals.

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Optogenetic manipulation of Gq- and Gi/o-coupled receptor signaling in neurons and heart muscle cells

Cited by 2 publications

References 76 publications

Active state structures of a bistable visual opsin bound to G proteins

Active state structures of a bistable visual opsin bound to G proteins

Activating an invertebrate bistable opsin with the all-trans 6.11 retinal analogue

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