Institut des Neurosciences Cellulaires et Integratives, UPR 3212, 5 rue Blaise Pascal, F-67000 Strasbourg, France.
Institut des Neurosciences Cellulaires et Integratives, UPR 3212, 5 rue Blaise Pascal, F-67000 Strasbourg, France.
Neurosci Biobehav Rev. 2019 Nov;106:73-90. doi: 10.1016/j.neubiorev.2018.09.026. Epub 2018 Sep 29.
G protein-coupled receptors (GPCR) represent the largest family of membrane proteins in the human genome. Physical association between two different GPCRs is linked to functional interactions which generates a novel entity, called heteromer, with specific ligand binding and signaling properties. Heteromerization is increasingly recognized to take place in the mesocorticolimbic pathway and to contribute to various aspects related to substance use disorder. This review focuses on heteromers identified in brain areas relevant to drug addiction. We report changes at the molecular and cellular levels that establish specific functional impact and highlight behavioral outcome in preclinical models. Finally, we briefly discuss selective targeting of native heteromers as an innovative therapeutic option.
G 蛋白偶联受体（GPCR）是人类基因组中最大的膜蛋白家族。两种不同 GPCR 之间的物理关联与功能相互作用有关，产生了一种新的实体，称为异源二聚体，具有特定的配体结合和信号转导特性。异源二聚体化越来越被认为发生在中边缘通路中，并有助于与物质使用障碍相关的各个方面。本综述重点介绍了与药物成瘾相关的大脑区域中鉴定的异源二聚体。我们报告了在分子和细胞水平上的变化，这些变化确立了特定的功能影响，并强调了临床前模型中的行为结果。最后，我们简要讨论了作为一种创新治疗选择的天然异源二聚体的选择性靶向。
