Research ArticleGPCR SIGNALING

Plasma membrane localization of the μ-opioid receptor controls spatiotemporal signaling

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Science Signaling  09 Feb 2016:
Vol. 9, Issue 414, pp. ra16
DOI: 10.1126/scisignal.aac9177

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Spatiotemporal opioid receptor signaling

The μ-opioid receptor (MOR) is a GPCR that mediates the effects of endogenous opioids and opioid analgesics, such as morphine. Different MOR agonists produce different biological effects, in part by differentially regulating receptor phosphorylation and internalization. In cells transfected with MOR, Halls et al. examined downstream signaling in the absence of receptor internalization. Whereas the synthetic opioid DAMGO stimulated receptor movement within the plasma membrane and transiently increased ERK activity in both the cytosol and nucleus, morphine stimulated a protein kinase C–dependent pathway that restricted MOR movement and produced prolonged cytosolic ERK activity. Similar effects were observed in mouse dorsal root ganglion neurons, suggesting that the differences in plasma membrane mobility or clustering of MOR may underlie the differential effects of its agonists in vivo.

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