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  Optical regulation of class C GPCRs by photoswitchable orthogonal remotely tethered ligands

Acosta-Ruiz, A., Broichhagen, J., & Levitz, J. (2019). Optical regulation of class C GPCRs by photoswitchable orthogonal remotely tethered ligands. In M. Tiberi (Ed.), G Protein-Coupled Receptor Signaling (pp. 103-136). New York, NY: Springer New York.

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Item Permalink: http://hdl.handle.net/21.11116/0000-0003-7DBB-F Version Permalink: http://hdl.handle.net/21.11116/0000-0005-6233-3
Genre: Book Chapter

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Tiberi_2019_GProtein-CoupledReceptorSignaling_103.pdf (Any fulltext), 706KB
 
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 Creators:
Acosta-Ruiz, Amanda, Author
Broichhagen, Johannes1, Author              
Levitz, Joshua, Author
Affiliations:
1Chemical Biology, Max Planck Institute for Medical Research, Max Planck Society, ou_2364732              

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Free keywords: Optogenetics; Photopharmacology; Tethered ligands; G protein-coupled receptors; Metabotropic glutamate receptors; PORTLs; Neuromodulation; SNAP tag
 Abstract: G protein-coupled receptors (GPCRs) respond to a wide range of extracellular cues to initiate complex downstream signaling cascades that control myriad aspects of cell function. Despite a long-standing appreciation of their importance to both basic physiology and disease treatment, it remains a major challenge to understand the dynamic activation patterns of GPCRs and the mechanisms by which they modulate biological processes at the molecular, cellular, and tissue levels. Unfortunately, classical methods of pharmacology and genetic knockout are often unable to provide the requisite precision needed to probe such questions. This is an especially pressing challenge for the class C GPCR family which includes receptors for the major excitatory and inhibitory neurotransmitters, glutamate and GABA, which signal in a rapid, spatially-delimited manner and contain many different subtypes whose roles are difficult to disentangle. The desire to manipulate class C GPCRs with spatiotemporal precision, genetic targeting, and subtype specificity has led to the development of a variety of photopharmacological tools. Of particular promise are the photoswitchable orthogonal remotely tethered ligands (“PORTLs”) which attach to self-labeling tags that are genetically encoded into full length, wild-type metabotropic glutamate receptors (mGluRs) and allow the receptor to be liganded and un-liganded in response to different wavelengths of illumination. While powerful for studying class C GPCRs, a number of detailed considerations must be made when working with these tools. The protocol included here should provide a basis for the development, characterization, optimization, and application of PORTLs for a wide range of GPCRs.

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Language(s): eng - English
 Dates: 2019-04-11
 Publication Status: Published in print
 Pages: 34
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: DOI: 10.1007/978-1-4939-9121-1_6
 Degree: -

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Title: G Protein-Coupled Receptor Signaling
Source Genre: Book
 Creator(s):
Tiberi, Mario, Editor
Affiliations:
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Publ. Info: New York, NY : Springer New York
Pages: 406 Volume / Issue: - Sequence Number: - Start / End Page: 103 - 136 Identifier: ISBN: 978-1-4939-9121-1