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Biased signaling at mu opioid receptor splice variants

Published on May 31, 2020   42 min

A selection of talks on Biochemistry

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My name is Ying-Xian Pan, I'm a member of the Department of Neurology at the Memorial Sloan-Kettering Cancer Center. My research interests have long focused on GPCRs, particularly the mu opioid receptors. Today, I will talk about biased signaling at the mu opioid receptor splice variants.
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Earlier pharmacological studies defined three types of opiate receptors, mu, kappa and delta. Molecular cloning led to identification of their corresponding genes OPRM1, OPRK1, and OPRD1, and their receptor proteins MOR-1 (MOP), KOR-1 (KOP) and DOR-1 (DOP). There is a fourth member of the opioid receptor gene family, OPRN1, encoding ORL-1 or NOP. Structurally, NOP shares high homology with the other three opioid receptors, but does not bind to any opiate. The crystal structures of all four receptors were resolved and published in the same issue of Nature in 2012. The mu opioid receptor has a special place in the opioid receptor family, because it mediates the actions of most of the clinically-used opioids such as morphine, fentanyl and methadone, as well as heroin. Mu opioid agonists can effectively relieve pain, mainly severe pain such as that caused by cancer. However, they also cause many side-effects including tolerance, physical dependence, respiratory depression, addiction and so on. Our goal is to understand the molecular mechanisms of opioid actions, and we hope to develop better analgesic drugs with limited side-effects.
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Biased signaling at mu opioid receptor splice variants

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