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BRET biosensors to study GPCR biology, pharmacology, and signal transduction.

Publication ,  Journal Article
Salahpour, A; Espinoza, S; Masri, B; Lam, V; Barak, LS; Gainetdinov, RR
Published in: Front Endocrinol (Lausanne)
2012

Bioluminescence resonance energy transfer (BRET)-based biosensors have been extensively used over the last decade to study protein-protein interactions and intracellular signal transduction in living cells. In this review, we discuss the various BRET biosensors that have been developed to investigate biology, pharmacology, and signaling of G protein-coupled receptors (GPCRs). GPCRs form two distinct types of multiprotein signal transduction complexes based upon their inclusion of G proteins or β-arrestins that can be differentially affected by drugs that exhibit functional selectivity toward G protein or β-arrestin signaling. BRET has been especially adept at illuminating the dynamics of protein-protein interactions between receptors, G proteins, β-arrestins, and their many binding partners in living cells; as well as measuring the formation and accumulation of second messengers following receptor activation. Specifically, we discuss in detail the application of BRET to study dopamine and trace amine receptors signaling, presenting examples of an exchange protein activated by cAMP biosensor to measure cAMP, β-arrestin biosensors to determine β-arrestin recruitment to the receptor, and dopamine D2 receptor and trace amine-associated receptor 1 biosensors to investigate heterodimerization between them. As the biochemical spectrum of BRET biosensors expands, the number of signaling pathways that can be measured will concomitantly increase. This will be particularly useful for the evaluation of functional selectivity in which the real-time BRET capability to measure distinct signaling modalities will dramatically shorten the time to characterize new generation of biased drugs. These emerging approaches will further expand the growing application of BRET in the screening for novel pharmacologically active compounds.

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Published In

Front Endocrinol (Lausanne)

DOI

EISSN

1664-2392

Publication Date

2012

Volume

3

Start / End Page

105

Location

Switzerland

Related Subject Headings

  • 3202 Clinical sciences
  • 1111 Nutrition and Dietetics
  • 1103 Clinical Sciences
 

Citation

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Salahpour, A., Espinoza, S., Masri, B., Lam, V., Barak, L. S., & Gainetdinov, R. R. (2012). BRET biosensors to study GPCR biology, pharmacology, and signal transduction. Front Endocrinol (Lausanne), 3, 105. https://doi.org/10.3389/fendo.2012.00105
Salahpour, Ali, Stefano Espinoza, Bernard Masri, Vincent Lam, Larry S. Barak, and Raul R. Gainetdinov. “BRET biosensors to study GPCR biology, pharmacology, and signal transduction.Front Endocrinol (Lausanne) 3 (2012): 105. https://doi.org/10.3389/fendo.2012.00105.
Salahpour A, Espinoza S, Masri B, Lam V, Barak LS, Gainetdinov RR. BRET biosensors to study GPCR biology, pharmacology, and signal transduction. Front Endocrinol (Lausanne). 2012;3:105.
Salahpour, Ali, et al. “BRET biosensors to study GPCR biology, pharmacology, and signal transduction.Front Endocrinol (Lausanne), vol. 3, 2012, p. 105. Pubmed, doi:10.3389/fendo.2012.00105.
Salahpour A, Espinoza S, Masri B, Lam V, Barak LS, Gainetdinov RR. BRET biosensors to study GPCR biology, pharmacology, and signal transduction. Front Endocrinol (Lausanne). 2012;3:105.

Published In

Front Endocrinol (Lausanne)

DOI

EISSN

1664-2392

Publication Date

2012

Volume

3

Start / End Page

105

Location

Switzerland

Related Subject Headings

  • 3202 Clinical sciences
  • 1111 Nutrition and Dietetics
  • 1103 Clinical Sciences