Fusion with Promiscuous G alpha(16) Subunit Reveals Signaling Bias at Muscarinic Receptors

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F67985823%3A_____%2F21%3A00546460" target="_blank" >RIV/67985823:_____/21:00546460 - isvavai.cz</a>

Result on the web

<a href="https://www.mdpi.com/1422-0067/22/18/10089" target="_blank" >https://www.mdpi.com/1422-0067/22/18/10089</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3390/ijms221810089" target="_blank" >10.3390/ijms221810089</a>

Result language

angličtina

Original language name

Fusion with Promiscuous G alpha(16) Subunit Reveals Signaling Bias at Muscarinic Receptors

Original language description

A complex evaluation of agonist bias at G-protein coupled receptors at the level of G-protein classes and isoforms including non-preferential ones is essential for advanced agonist screening and drug development. Molecular crosstalk in downstream signaling and a lack of sufficiently sensitive and selective methods to study direct coupling with G-protein of interest complicates this analysis. We performed binding and functional analysis of 11 structurally different agonists on prepared fusion proteins of individual subtypes of muscarinic receptors and non-canonical promiscuous alpha-subunit of G(16) protein to study agonist bias. We have demonstrated that fusion of muscarinic receptors with G alpha(16) limits access of other competitive G alpha subunits to the receptor, and thus enables us to study activation of G alpha(16) mediated pathway more specifically. Our data demonstrated agonist-specific activation of G(16) pathway among individual subtypes of muscarinic receptors and revealed signaling bias of oxotremorine towards G alpha(16) pathway at the M-2 receptor and at the same time impaired G alpha(16) signaling of iperoxo at M-5 receptors. Our data have shown that fusion proteins of muscarinic receptors with alpha-subunit of G-proteins can serve as a suitable tool for studying agonist bias, especially at non-preferential pathways.

Czech name

—

Czech description

—

Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

30104 - Pharmacology and pharmacy

Project

<a href="/en/project/GJ19-06106Y" target="_blank" >GJ19-06106Y: Analysis of signalling bias of novel synthetic muscarinic agonists</a><br>

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year

2021

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

International Journal of Molecular Sciences

ISSN

1422-0067

e-ISSN

1422-0067

Volume of the periodical

22

Issue of the periodical within the volume

18

Country of publishing house

CH - SWITZERLAND

Number of pages

20

Pages from-to

10089

UT code for WoS article

000699826600001

EID of the result in the Scopus database

2-s2.0-85115086361