Journal
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Volume 643, Issue -, Pages 96-104Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2022.12.077
Keywords
?-opioid receptor; Posttranslational modification; Tolerance; Phosphorylation; Ubiquitination
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Previous studies have focused on phosphorylation of the mu-opioid receptor to maintain cellular sensitivity, while recent attention has shifted towards ubiquitination as a form of posttranslational modification. In this study, a ubiquitination-deficient mutant of the mu-opioid receptor was generated to investigate its role in analgesic signaling, desensitization, and internalization. The findings suggest that ubiquitination is not essential for the Gi/o pathway and receptor phosphorylation, but instead regulates the internalization efficiency of the desensitized MOP.
Opioids are highly potent analgesics but develop tolerance. Previous studies have focused on phosphorylation of the mu-opioid receptor as it is involved in maintaining cellular sensitivity via desensitization, recycling, and degradation of the activated receptor. Recently, ubiquitination, another form of posttranslational modification has attracted attention in terms of triggering intracellular signaling and regulation of the activated receptor. Here, we generated a ubiquitination-deficient mutant of the mu-opioid receptor to investigate whether ubiquitination is involved in driving Gi/o-mediated analgesic signaling, receptor desensitization or subsequent receptor internalization. Our study shows that the Gi/o pathway and receptor phosphorylation do not require ubiquitination. Instead, ubiquitination regulates the internalization efficiency and might help in promoting internalization of the desensitized MOP.(c) 2022 Elsevier Inc. All rights reserved.
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