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Publication : Selective targeting of mu opioid receptors to primary cilia.

First Author  Fagan RR Year  2024
Journal  Cell Rep Volume  43
Issue  5 Pages  114164
PubMed ID  38678559 Mgi Jnum  J:350672
Mgi Id  MGI:7658765 Doi  10.1016/j.celrep.2024.114164
Citation  Fagan RR, et al. (2024) Selective targeting of mu opioid receptors to primary cilia. Cell Rep 43(5):114164
abstractText  Opioid receptors are therapeutically important G protein-coupled receptors (GPCRs) with diverse neuromodulatory effects. The functional consequences of opioid receptor activation are known to depend on receptor location in the plasma membrane, but mechanisms mediating selective localization of receptors to any particular membrane domain remain elusive. Here, we demonstrate the targeting of the mu opioid receptor (MOR) to the primary cilium, a discrete microdomain of the somatic plasma membrane, both in vivo and in cultured cells. We further show that ciliary targeting is specific to MORs, requires a 17-residue sequence unique to the MOR cytoplasmic tail, and additionally requires the Tubby-like protein 3 (TULP3) ciliary adaptor protein. Our results reveal the potential for opioid receptors to undergo selective localization to the primary cilium. We propose that ciliary targeting is mediated through an elaboration of the recycling pathway, directed by a specific C-terminal recycling sequence in cis and requiring TULP3 in trans.
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