beta-Arrestin 1 and 2 similarly influence mu-opioid receptor mobility and distinctly modulate adenylyl cyclase activity
The result's identifiers
Result code in 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>
Result on the web
<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>
Alternative languages
Result language
angličtina
Original language name
beta-Arrestin 1 and 2 similarly influence mu-opioid receptor mobility and distinctly modulate adenylyl cyclase activity
Original language description
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.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30105 - Physiology (including cytology)
Result continuities
Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)<br>S - Specificky vyzkum na vysokych skolach
Others
Publication year
2021
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Cellular Signalling
ISSN
0898-6568
e-ISSN
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Volume of the periodical
87
Issue of the periodical within the volume
November
Country of publishing house
US - UNITED STATES
Number of pages
10
Pages from-to
110124
UT code for WoS article
000702705800008
EID of the result in the Scopus database
2-s2.0-85113786021