PDF(Pubmed)
Abstract：
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.
摘要：
阿片类受体是治疗上重要的G蛋白偶联受体（GPCRs），具有多种神经调节作用。已知阿片受体激活的功能后果取决于受体在质膜中的位置，但是介导受体选择性定位到任何特定膜结构域的机制仍然难以捉摸。这里,我们证明了μ阿片受体（MOR）靶向初级纤毛，体细胞质膜的离散微区，在体内和培养细胞中。我们进一步表明纤毛靶向是MORs特异性的，需要MOR细胞质尾特有的17个残基序列，并且另外需要Tubby样蛋白3(TULP3)纤毛衔接蛋白。我们的结果揭示了阿片受体选择性定位到初级纤毛的潜力。我们认为纤毛靶向是通过对再循环途径的阐述来介导的，由顺式的特定C端再循环序列指导，并要求反式的TULP3。
