Aznar Nicolas, Kalogriopoulos Nicholas, Midde Krishna K, Ghosh Pradipta
Department of Medicine, University of California at San Diego, La Jolla, CA, USA.
Department of Cell and Molecular Medicine, University of California at San Diego, La Jolla, CA, USA.
Bioessays. 2016 Apr;38(4):379-93. doi: 10.1002/bies.201500133. Epub 2016 Feb 16.
Canonical signal transduction via heterotrimeric G proteins is spatially and temporally restricted, that is, triggered exclusively at the plasma membrane (PM), only by agonist activation of G protein-coupled receptors (GPCRs) via a process that completes within a few hundred milliseconds. Recently, a rapidly emerging paradigm has revealed a non-canonical pathway for activation of heterotrimeric G proteins by the non-receptor guanidine-nucleotide exchange factor (GEF), GIV/Girdin. This pathway has distinctive temporal and spatial features and an unusual profile of receptor engagement: diverse classes of receptors, not just GPCRs can engage with GIV to trigger such activation. Such activation is spatially and temporally unrestricted, that is, can occur both at the PM and on internal membranes discontinuous with the PM, and can continue for prolonged periods of time. Here, we provide the most complete up-to-date review of the molecular mechanisms that govern the unique spatiotemporal aspects of non-canonical G protein activation by GIV and the relevance of this new paradigm in health and disease.
通过异源三聚体G蛋白进行的经典信号转导在空间和时间上受到限制，也就是说，仅在质膜（PM）上由G蛋白偶联受体（GPCR）通过在几百毫秒内完成的过程进行激动剂激活而触发。最近，一个迅速出现的范例揭示了一种非经典途径，即由非受体鸟苷酸交换因子（GEF）GIV/Girdin激活异源三聚体G蛋白。该途径具有独特的时间和空间特征以及不同寻常的受体参与模式：不仅GPCR，多种类型的受体都可以与GIV结合以触发这种激活。这种激活在空间和时间上不受限制，也就是说，可以发生在质膜以及与质膜不连续的内膜上，并且可以持续很长时间。在这里，我们提供了关于GIV调控非经典G蛋白激活独特时空方面的分子机制以及这一新范例在健康和疾病中的相关性的最完整的最新综述。
