The Dynamics of GPCR Oligomerization and Their Functional Consequences

Sleno, Rory; Hébert, Terence E.

doi:10.1016/bs.ircmb.2018.02.005

Cited by 42 publications

(31 citation statements)

References 139 publications

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“…Association between GPCRs, either in the form of dimers or oligomers, plays a pivotal role in GPCR function, influencing intracellular trafficking, ligand binding, and signaling regulation ( 66 – 68 ). In the case of the FSHR, the receptor self-associates early during receptor biosynthesis, and using both biochemical and super-resolution imaging approaches evidence supports the quaternary association at the PM as both monomers and higher order structures (dimers and oligomers) ( 13 , 69 , 70 ).…”

Section: Domains and Motifs Involved In Fshr Upward Traffickingmentioning

confidence: 99%

Structure-Function Relationships of the Follicle-Stimulating Hormone Receptor

et al. 2018

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The follicle-stimulating hormone receptor (FSHR) plays a crucial role in reproduction. This structurally complex receptor is a member of the G-protein coupled receptor (GPCR) superfamily of membrane receptors. As with the other structurally similar glycoprotein hormone receptors (the thyroid-stimulating hormone and luteinizing hormone-chorionic gonadotropin hormone receptors), the FSHR is characterized by an extensive extracellular domain, where binding to FSH occurs, linked to the signal specificity subdomain or hinge region. This region is involved in ligand-stimulated receptor activation whereas the seven transmembrane domain is associated with receptor activation and transmission of the activation process to the intracellular loops comprised of amino acid sequences, which predicate coupling to effectors, interaction with adapter proteins, and triggering of downstream intracellular signaling. In this review, we describe the most important structural features of the FSHR intimately involved in regulation of FSHR function, including trafficking, dimerization, and oligomerization, ligand binding, agonist-stimulated activation, and signal transduction.

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Section: Domains and Motifs Involved In Fshr Upward Traffickingmentioning

confidence: 99%

Structure-Function Relationships of the Follicle-Stimulating Hormone Receptor

et al. 2018

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“…This is especially critical as GPCR homo-and hetero-multimerization remains a controversial topic that may have major implications for general physiology and drug discovery. 33 We decided to use our labelling probes in conjunction with single molecule pulldown (SiMPull), a strategy which allows single receptor complexes to be isolated and imaged for analysis of stoichiometry via counting of uorophore bleaching steps. 34 To probe a prototypical class C GPCR, reported to form constitutive dimers by most studies to date, 35,36 we used HA-SNAP-mGluR2.…”

Section: Resultsmentioning

confidence: 99%

Interrogating surface versus intracellular transmembrane receptor populations using cell-impermeable SNAP-tag substrates

et al. 2020

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“…Fluorescence-based methods have been widely used for assessing GPCR dimer-and oligomerization but rarely distinguish between surface and intracellular pools which may lead to confounding results and discrepancies across studies. This is especially critical as GPCR homo-and hetero-multimerization remains a controversial topic that may have major implications for general physiology and drug discovery 33 . We decided to use our labeling probes in conjunction with single molecule pulldown ("SiMPull") a strategy which allows single receptor complexes to be isolated and imaged for analysis of stoichiometry via counting of fluorophore bleaching steps 34 .…”

Section: Resultsmentioning

confidence: 99%

Interrogating surface versus intracellular transmembrane receptor populations using cell-impermeable SNAP-tag substrates

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Gutzeit

Ast

et al. 2020

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Employing self-labelling protein tags for the attachment of fluorescent dyes has become a routine and powerful technique in optical microscopy to visualize and track fused proteins. However, membrane permeability of the dyes and the associated background signals can interfere with the analysis of extracellular labeling sites. Here we describe a novel approach to improve extracellular labeling by functionalizing the SNAP-tag substrate benzyl guanine ("BG") with a charged sulfonate ("SBG"). This chemical manipulation improves solubility, reduces non-specific staining and renders the bioconjugation handle impermeable while leaving its cargo untouched. We report SBG-conjugated fluorophores across the visible spectrum, which cleanly label SNAP-fused proteins in the plasma membrane of living cells. We demonstrate the utility of SBG-conjugated fluorophores to interrogate class A, B and C G protein-coupled receptors (GPCRs) using a range of imaging approaches including nanoscopic super-resolution imaging, analysis of GPCR trafficking from intra-and extracellular pools, in vivo labelling in mouse brain and analysis of receptor stoichiometry using single molecule pull down.

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The Dynamics of GPCR Oligomerization and Their Functional Consequences

Cited by 42 publications

References 139 publications

Structure-Function Relationships of the Follicle-Stimulating Hormone Receptor

Structure-Function Relationships of the Follicle-Stimulating Hormone Receptor

Interrogating surface versus intracellular transmembrane receptor populations using cell-impermeable SNAP-tag substrates

Interrogating surface versus intracellular transmembrane receptor populations using cell-impermeable SNAP-tag substrates

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