The in vivo chemistry of photoswitched tethered ligands

Broichhagen, Johannes; Trauner, Dirk

doi:10.1016/j.cbpa.2014.07.008

Cited by 56 publications

(62 citation statements)

References 31 publications

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“…The reversible change of the photoisomerizable group from all-trans to cis configuration controlled by light alters the ability of the ligand to block/unblock channels or to activate/inactivate receptors. Currently, azobenzenes have been the choice for the photoisomerizable group (Broichhagen & Trauner 2014). Optopharmacological photoswitches have been developed to regulate membrane channels (Polosukhina et al 2012, Tochitsky et al 2014) and ligand-gated receptors such as GABA receptors (Yue et al 2012) and glutamate receptors (Adesnik et al 2005, Volgraf et al 2007).…”

Section: Chemical-based Photoswitchesmentioning

confidence: 99%

Optogenetic Approaches to Restoring Vision

Pan

2015

Annu. Rev. Vis. Sci.

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Severe loss of photoreceptor cells in inherited or acquired retinal degenerative diseases can result in partial loss of sight or complete blindness. The optogenetic strategy for restoration of vision utilizes optogenetic tools to convert surviving inner retinal neurons into photosensitive cells; thus, light sensitivity is imparted to the retina after the death of photoreceptor cells. Proof-of-concept studies, especially those using microbial rhodopsins, have demonstrated restoration of light responses in surviving retinal neurons and visually guided behaviors in animal models. Significant progress has also been made in improving microbial rhodopsin-based optogenetic tools, developing virus-mediated gene delivery, and targeting specific retinal neurons and subcellular compartments of retinal ganglion cells. In this article, we review the current status of the field and outline further directions and challenges to the advancement of this strategy toward clinical application and improvement in the outcomes of restored vision.

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Section: Chemical-based Photoswitchesmentioning

confidence: 99%

Optogenetic Approaches to Restoring Vision

Pan

2015

Annu. Rev. Vis. Sci.

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“…Genetic targeting can be achieved with Photoswitchable tethered ligands (PTL). PTLs are photosensitive ligands that will covalently bind to an engineered protein [4]. This approach was developed for metabotropic glutamate receptors (LimGluR), but could be translation to another GPCRs [73].…”

Section: Photopharmacologymentioning

confidence: 99%

“…Current advances in optogenetics target specific members of canonical GPCR signaling pathways with both natural and engineered optically sensitive proteins. Additionally, endogenous receptors are targeted by photoactivatable ligands, a method called photopharmacology [4,8]. Furthermore, other optogenetic approaches utilize genetically encoded reporters of protein-protein interactions or the production of second messengers [9].…”

Section: Introductionmentioning

confidence: 99%

Optogenetic approaches for dissecting neuromodulation and GPCR signaling in neural circuits

Spangler

Bruchas

2017

Current Opinion in Pharmacology

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Optogenetics has revolutionized neuroscience by providing means to control cell signaling with spatiotemporal control in discrete cell types. In this review, we summarize four major classes of optical tools to manipulate neuromodulatory GPCR signaling: opsins (including engineered chimeric receptors); photoactivatable proteins; photopharmacology through caging - photoswitchable molecules; fluorescent protein based reporters and biosensors. Additionally, we highlight technologies to utilize these tools in vitro and in vivo, including Cre dependent viral vector expression and two-photon microscopy. These emerging techniques targeting specific members of the GPCR signaling pathway offer an expansive base for investigating GPCR signaling in behavior and disease states, in addition to paving a path to potential therapeutic developments.

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“…Photoisomerization of synthetic compounds has similarly been exploited to control protein function, exemplified by the modulation of ion channels and GPCRs with azobenzene-functionalized ligands (Fig. 5b–c) 65-67 . These photochromic probes have imparted switchable neuronal activity in wild type zebrafish, mouse, and rat models, complementing the application of channelrhodopsins and halorhodopsins in transgenic organisms.Anotherintriguingexampleofligand-basedopticalcontrolisoptovin,aphotoactivatable agonist of the transient receptor potential A1 (TRPA1) channel (Fig.…”

Section: Photoactivatable Probes Of Protein Functionmentioning

confidence: 99%

Illuminating developmental biology through photochemistry

Kowalik

Chen

2017

Nat Chem Biol

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Developmental biology has been continually shaped by technological advances, evolving from a descriptive science into one immersed in molecular and cellular mechanism. Most recently, genome sequencing and “omics” profiling have provided developmental biologists with a wealth of genetic and biochemical information; however, fully translating this knowledge into functional understanding will require new experimental capabilities. Photoactivatable probes have emerged as particularly valuable tools for investigating developmental mechanisms, as they can enable rapid, specific manipulations of DNA, RNA, proteins, and cells with spatiotemporal precision. In this perspective, we describe optochemical and optogenetic systems that have been applied in multicellular organisms, insights gained through these probes, and their current limitations. We also suggest how chemical biologists can expand the reach of photoactivatable technologies and bring new depth to our understanding of organismal development.

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The in vivo chemistry of photoswitched tethered ligands

Cited by 56 publications

References 31 publications

Optogenetic Approaches to Restoring Vision

Optogenetic Approaches to Restoring Vision

Optogenetic approaches for dissecting neuromodulation and GPCR signaling in neural circuits

Illuminating developmental biology through photochemistry

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