Specificity of olfactory receptor interactions with other G protein-coupled receptors
Specificity of olfactory receptor interactions with other G protein-coupled receptors
复制标题
DOI：
10.1074/jbc.m610781200
复制
发表时间：
2007-06-29
影响因子：
4.8
通讯作者：
Hall, Randy A.
中科院分区：
文献类型：
--
作者：
Bush, Cristina F.;Jones, Seth V.;Hall, Randy A.
嗅觉受体（OR）在异源细胞中的质膜定位差，阻碍了对OR药理学的研究。我们先前报道了与β 2-肾上腺素能受体（β 2-AR）的结合促进了OR M71在HEK-293细胞质膜上的功能性表达。在本研究中，我们研究了M71与其他G蛋白偶联受体（GPCR）相互作用的特异性。M71在HEK-293细胞中与42种不同的GPCR共表达，并且这些受体中的绝大多数对M71表面表达没有显著影响。然而，与三种嘌呤能受体亚型（P2 Y（1）R、P2 Y（2）R和A（2A）R）共表达导致M71的质膜定位显著增强。与P2 Y1 R和P2 Y2 R共表达的M71的激动剂刺激通过M71与G α（o）的偶联激活促分裂原活化蛋白激酶途径。我们还检测了β（2）-AR、P2 Y（1）R、P2 Y（2）R和A（2A）R与M71以外的OR相互作用和调节OR的能力。我们发现，β 2-AR或嘌呤能受体的共表达增强了M71亚家族成员的表面表达，但对不同亚家族的其他几个OR没有增强。此外，通过嵌合受体研究，我们确定β（2）-AR的第二个跨膜结构域是β（2）-AR促进M71质膜定位所必需的。这些研究揭示了OR与其他GPCR相互作用的特异性以及嗅觉受体运输的机制。
Studies on olfactory receptor ( OR) pharmacology have been hindered by the poor plasma membrane localization of most ORs in heterologous cells. We previously reported that association with the beta(2)-adrenergic receptor (beta(2)-AR) facilitates functional expression of the OR M71 at the plasma membrane of HEK-293 cells. In the present study, we examined the specificity of M71 interactions with other G protein-coupled receptors (GPCRs). M71 was co-expressed in HEK-293 cells with 42 distinct GPCRs, and the vast majority of these receptors had no significant effect on M71 surface expression. However, co-expression with three subtypes of purinergic receptor (P2Y(1)R, P2Y(2)R, and A(2A)R) resulted in markedly enhanced plasma membrane localization of M71. Agonist stimulation of M71 co-expressed with P2Y1R and P2Y2R activated the mitogen-activated protein kinase pathway via coupling of M71 to G alpha(o). We also examined the ability of beta(2)-AR, P2Y(1)R, P2Y(2)R, and A(2A)R to interact with and regulate ORs beyond M71. We found that coexpression of beta(2)-AR or the purinergic receptors enhanced the surface expression for an M71 subfamily member but not for several other ORs from different subfamilies. In addition, through chimeric receptor studies, we determined that the second transmembrane domain of beta(2)-AR is necessary for beta(2)-AR facilitation of M71 plasma membrane localization. These studies shed light on the specificity of OR interactions with other GPCRs and the mechanisms governing olfactory receptor trafficking.