beta-Arrestin 1 and 2 similarly influence mu-opioid receptor mobility and distinctly modulate adenylyl cyclase activity

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11310%2F21%3A10437984" target="_blank" >RIV/00216208:11310/21:10437984 - isvavai.cz</a>

Výsledek na webu

<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=~hA_EU~8CL" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=~hA_EU~8CL</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.cellsig.2021.110124" target="_blank" >10.1016/j.cellsig.2021.110124</a>

Jazyk výsledku

angličtina

Název v původním jazyce

beta-Arrestin 1 and 2 similarly influence mu-opioid receptor mobility and distinctly modulate adenylyl cyclase activity

Popis výsledku v původním jazyce

beta-Arrestins are known to play a crucial role in GPCR-mediated transmembrane signaling processes. However, there are still many unanswered questions, especially those concerning the presumed similarities and differences of beta-arrestin isoforms. Here, we examined the roles of beta-arrestin 1 and beta-arrestin 2 at different levels of mu-opioid receptor (MOR)-regulated signaling, including MOR mobility, internalization of MORs, and adenylyl cyclase (AC) activity. For this purpose, naive HEK293 cells or HEK293 cells stably expressing YFP-tagged MOR were transfected with appropriate siRNAs to block in a specific way the expression of beta-arrestin 1 or beta-arrestin 2. We did not find any significant differences in the ability of beta-arrestin isoforms to influence the lateral mobility of MORs in the plasma membrane. Using FRAP and line-scan FCS, we observed that knockdown of both beta-arrestins similarly increased MOR lateral mobility and diminished the ability of DAMGO and endomorphin-2, respectively, to enhance and slow down receptor diffusion kinetics. However, beta-arrestin 1 and beta-arrestin 2 diversely affected the process of agonist-induced MOR endocytosis and exhibited distinct modulatory effects on AC function. Knockdown of beta-arrestin 1, in contrast to beta-arrestin 2, more effectively suppressed forskolin-stimulated AC activity and prevented the ability of activated-MORs to inhibit the enzyme activity. Moreover, we have demonstrated for the first time that beta-arrestin 1, and partially beta-arrestin 2, may somehow interact with AC and that this interaction is strongly supported by the enzyme activation. These data provide new insights into the functioning of beta-arrestin isoforms and their distinct roles in GPCR-mediated signaling.

Název v anglickém jazyce

beta-Arrestin 1 and 2 similarly influence mu-opioid receptor mobility and distinctly modulate adenylyl cyclase activity

Popis výsledku anglicky

beta-Arrestins are known to play a crucial role in GPCR-mediated transmembrane signaling processes. However, there are still many unanswered questions, especially those concerning the presumed similarities and differences of beta-arrestin isoforms. Here, we examined the roles of beta-arrestin 1 and beta-arrestin 2 at different levels of mu-opioid receptor (MOR)-regulated signaling, including MOR mobility, internalization of MORs, and adenylyl cyclase (AC) activity. For this purpose, naive HEK293 cells or HEK293 cells stably expressing YFP-tagged MOR were transfected with appropriate siRNAs to block in a specific way the expression of beta-arrestin 1 or beta-arrestin 2. We did not find any significant differences in the ability of beta-arrestin isoforms to influence the lateral mobility of MORs in the plasma membrane. Using FRAP and line-scan FCS, we observed that knockdown of both beta-arrestins similarly increased MOR lateral mobility and diminished the ability of DAMGO and endomorphin-2, respectively, to enhance and slow down receptor diffusion kinetics. However, beta-arrestin 1 and beta-arrestin 2 diversely affected the process of agonist-induced MOR endocytosis and exhibited distinct modulatory effects on AC function. Knockdown of beta-arrestin 1, in contrast to beta-arrestin 2, more effectively suppressed forskolin-stimulated AC activity and prevented the ability of activated-MORs to inhibit the enzyme activity. Moreover, we have demonstrated for the first time that beta-arrestin 1, and partially beta-arrestin 2, may somehow interact with AC and that this interaction is strongly supported by the enzyme activation. These data provide new insights into the functioning of beta-arrestin isoforms and their distinct roles in GPCR-mediated signaling.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30105 - Physiology (including cytology)

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)<br>S - Specificky vyzkum na vysokych skolach

Rok uplatnění

2021

Kód důvěrnosti údajů

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

Název periodika

Cellular Signalling

ISSN

0898-6568

e-ISSN

—

Svazek periodika

87

Číslo periodika v rámci svazku

November

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

10

Strana od-do

110124

Kód UT WoS článku

000702705800008

EID výsledku v databázi Scopus

2-s2.0-85113786021