Effector membrane translocation biosensors reveal G protein and βarrestin coupling profiles of 100 therapeutically relevant GPCRs

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt

Standard

Effector membrane translocation biosensors reveal G protein and βarrestin coupling profiles of 100 therapeutically relevant GPCRs. / Avet, Charlotte; Mancini, Arturo; Breton, Billy; Le Gouill, Christian; Hauser, Alexander S.; Normand, Claire; Kobayashi, Hiroyuki; Gross, Florence; Hogue, Mireille; Lukasheva, Viktoriya; St-Onge, Stéphane; Carrier, Marilyn; Héroux, Madeleine; Morissette, Sandra; Fauman, Eric B.; Fortin, Jean Philippe; Schann, Stephan; Leroy, Xavier; Gloriam, David E.; Bouvier, Michel.

I: eLife, Bind 11, e74101, 2022.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt

Harvard

Avet, C, Mancini, A, Breton, B, Le Gouill, C, Hauser, AS, Normand, C, Kobayashi, H, Gross, F, Hogue, M, Lukasheva, V, St-Onge, S, Carrier, M, Héroux, M, Morissette, S, Fauman, EB, Fortin, JP, Schann, S, Leroy, X, Gloriam, DE & Bouvier, M 2022, 'Effector membrane translocation biosensors reveal G protein and βarrestin coupling profiles of 100 therapeutically relevant GPCRs', eLife, bind 11, e74101. https://doi.org/10.7554/eLife.74101

APA

Avet, C., Mancini, A., Breton, B., Le Gouill, C., Hauser, A. S., Normand, C., Kobayashi, H., Gross, F., Hogue, M., Lukasheva, V., St-Onge, S., Carrier, M., Héroux, M., Morissette, S., Fauman, E. B., Fortin, J. P., Schann, S., Leroy, X., Gloriam, D. E., & Bouvier, M. (2022). Effector membrane translocation biosensors reveal G protein and βarrestin coupling profiles of 100 therapeutically relevant GPCRs. eLife, 11, [e74101]. https://doi.org/10.7554/eLife.74101

Vancouver

Avet C, Mancini A, Breton B, Le Gouill C, Hauser AS, Normand C o.a. Effector membrane translocation biosensors reveal G protein and βarrestin coupling profiles of 100 therapeutically relevant GPCRs. eLife. 2022;11. e74101. https://doi.org/10.7554/eLife.74101

Author

Avet, Charlotte ; Mancini, Arturo ; Breton, Billy ; Le Gouill, Christian ; Hauser, Alexander S. ; Normand, Claire ; Kobayashi, Hiroyuki ; Gross, Florence ; Hogue, Mireille ; Lukasheva, Viktoriya ; St-Onge, Stéphane ; Carrier, Marilyn ; Héroux, Madeleine ; Morissette, Sandra ; Fauman, Eric B. ; Fortin, Jean Philippe ; Schann, Stephan ; Leroy, Xavier ; Gloriam, David E. ; Bouvier, Michel. / Effector membrane translocation biosensors reveal G protein and βarrestin coupling profiles of 100 therapeutically relevant GPCRs. I: eLife. 2022 ; Bind 11.

Bibtex

@article{458a7641d32d480d8d940fdacae588c1,
title = "Effector membrane translocation biosensors reveal G protein and βarrestin coupling profiles of 100 therapeutically relevant GPCRs",
abstract = "The recognition that individual GPCRs can activate multiple signaling pathways has raised the possibility of developing drugs selectively targeting therapeutically relevant ones. This requires tools to determine which G proteins and βarrestins are activated by a given receptor. Here, we present a set of BRET sensors monitoring the activation of the 12 G protein subtypes based on the translocation of their effectors to the plasma membrane (EMTA). Unlike most of the existing detection systems, EMTA does not require modification of receptors or G proteins (except for Gs). EMTA was found to be suitable for the detection of constitutive activity, inverse agonism, biased signaling and polypharmacology. Profiling of 100 therapeutically relevant human GPCRs resulted in 1500 pathway-specific concentration-response curves and revealed a great diversity of coupling profiles ranging from exquisite selectivity to broad promiscuity. Overall, this work describes unique resources for studying the complexities underlying GPCR signaling and pharmacology.",
keywords = "biochemistry, biosensor, chemical biology, effector membrane translocation assay, enhanced bystander bioluminescence resonance energy transfer, G protein activation, g protein-coupled receptor, high-throughput assay, human",
author = "Charlotte Avet and Arturo Mancini and Billy Breton and {Le Gouill}, Christian and Hauser, {Alexander S.} and Claire Normand and Hiroyuki Kobayashi and Florence Gross and Mireille Hogue and Viktoriya Lukasheva and St{\'e}phane St-Onge and Marilyn Carrier and Madeleine H{\'e}roux and Sandra Morissette and Fauman, {Eric B.} and Fortin, {Jean Philippe} and Stephan Schann and Xavier Leroy and Gloriam, {David E.} and Michel Bouvier",
note = "Publisher Copyright: {\textcopyright} 2022, Avet et al.",
year = "2022",
doi = "10.7554/eLife.74101",
language = "English",
volume = "11",
journal = "eLife",
issn = "2050-084X",
publisher = "eLife Sciences Publications Ltd.",

}

RIS

TY - JOUR

T1 - Effector membrane translocation biosensors reveal G protein and βarrestin coupling profiles of 100 therapeutically relevant GPCRs

AU - Avet, Charlotte

AU - Mancini, Arturo

AU - Breton, Billy

AU - Le Gouill, Christian

AU - Hauser, Alexander S.

AU - Normand, Claire

AU - Kobayashi, Hiroyuki

AU - Gross, Florence

AU - Hogue, Mireille

AU - Lukasheva, Viktoriya

AU - St-Onge, Stéphane

AU - Carrier, Marilyn

AU - Héroux, Madeleine

AU - Morissette, Sandra

AU - Fauman, Eric B.

AU - Fortin, Jean Philippe

AU - Schann, Stephan

AU - Leroy, Xavier

AU - Gloriam, David E.

AU - Bouvier, Michel

N1 - Publisher Copyright: © 2022, Avet et al.

PY - 2022

Y1 - 2022

N2 - The recognition that individual GPCRs can activate multiple signaling pathways has raised the possibility of developing drugs selectively targeting therapeutically relevant ones. This requires tools to determine which G proteins and βarrestins are activated by a given receptor. Here, we present a set of BRET sensors monitoring the activation of the 12 G protein subtypes based on the translocation of their effectors to the plasma membrane (EMTA). Unlike most of the existing detection systems, EMTA does not require modification of receptors or G proteins (except for Gs). EMTA was found to be suitable for the detection of constitutive activity, inverse agonism, biased signaling and polypharmacology. Profiling of 100 therapeutically relevant human GPCRs resulted in 1500 pathway-specific concentration-response curves and revealed a great diversity of coupling profiles ranging from exquisite selectivity to broad promiscuity. Overall, this work describes unique resources for studying the complexities underlying GPCR signaling and pharmacology.

AB - The recognition that individual GPCRs can activate multiple signaling pathways has raised the possibility of developing drugs selectively targeting therapeutically relevant ones. This requires tools to determine which G proteins and βarrestins are activated by a given receptor. Here, we present a set of BRET sensors monitoring the activation of the 12 G protein subtypes based on the translocation of their effectors to the plasma membrane (EMTA). Unlike most of the existing detection systems, EMTA does not require modification of receptors or G proteins (except for Gs). EMTA was found to be suitable for the detection of constitutive activity, inverse agonism, biased signaling and polypharmacology. Profiling of 100 therapeutically relevant human GPCRs resulted in 1500 pathway-specific concentration-response curves and revealed a great diversity of coupling profiles ranging from exquisite selectivity to broad promiscuity. Overall, this work describes unique resources for studying the complexities underlying GPCR signaling and pharmacology.

KW - biochemistry

KW - biosensor

KW - chemical biology

KW - effector membrane translocation assay

KW - enhanced bystander bioluminescence resonance energy transfer

KW - G protein activation

KW - g protein-coupled receptor

KW - high-throughput assay

KW - human

U2 - 10.7554/eLife.74101

DO - 10.7554/eLife.74101

M3 - Journal article

C2 - 35302493

AN - SCOPUS:85128487330

VL - 11

JO - eLife

JF - eLife

SN - 2050-084X

M1 - e74101

ER -

ID: 304783877