Terrillon Sonia, Bouvier Michel
Department of Biochemistry, Université de Montréal, C.P. 6128, succursale Centre-Ville, Montréal, Québec, Canada H3C 3J7.
EMBO Rep. 2004 Jan;5(1):30-4. doi: 10.1038/sj.embor.7400052.
The classical idea that G-protein-coupled receptors (GPCRs) function as monomeric entities has been unsettled by the emerging concept of GPCR dimerization. Recent findings have indicated not only that many GPCRs exist as homodimers and heterodimers, but also that their oligomeric assembly could have important functional roles. Several studies have shown that dimerization occurs early after biosynthesis, suggesting that it has a primary role in receptor maturation. G-protein coupling, downstream signalling and regulatory processes such as internalization have also been shown to be influenced by the dimeric nature of the receptors. In addition to raising fundamental questions about GPCR function, the concept of dimerization could be important in the development and screening of drugs that act through this receptor class. In particular, the changes in ligand-binding and signalling properties that accompany heterodimerization could give rise to an unexpected pharmacological diversity that would need to be considered.
G蛋白偶联受体(GPCRs)作为单体发挥作用的经典观点,已被新出现的GPCR二聚化概念所颠覆。最近的研究结果表明,许多GPCRs不仅以同二聚体和异二聚体形式存在,而且它们的寡聚体组装可能具有重要的功能作用。多项研究表明,二聚化在生物合成后不久就会发生,这表明它在受体成熟过程中起主要作用。G蛋白偶联、下游信号传导以及诸如内化等调节过程也已被证明会受到受体二聚体性质的影响。除了引发有关GPCR功能的基本问题外,二聚化概念在开发和筛选作用于这类受体的药物方面可能也很重要。特别是,异二聚化伴随的配体结合和信号特性变化可能会产生意想不到的药理学多样性,这需要加以考虑。