Moon Anne M, Stauffer Anna M, Schwindinger William F, Sheridan Kathy, Firment Ashley, Robishaw Janet D
The Weis Center for Research, Geisinger Clinic, Danville, Pennsylvania, United States of America.
PLoS One. 2014 Mar 5;9(3):e90970. doi: 10.1371/journal.pone.0090970. eCollection 2014.
Heterotrimeric G-proteins modulate many processes essential for embryonic development including cellular proliferation, migration, differentiation, and survival. Although most research has focused on identifying the roles of the various αsubtypes, there is growing recognition that similarly divergent βγ dimers also regulate these processes. In this paper, we show that targeted disruption of the mouse Gng5 gene encoding the γ5 subtype produces embryonic lethality associated with severe head and heart defects. Collectively, these results add to a growing body of data that identify critical roles for the γ subunits in directing the assembly of functionally distinct G-αβγ trimers that are responsible for regulating diverse biological processes. Specifically, the finding that loss of the G-γ5 subtype is associated with a reduced number of cardiac precursor cells not only provides a causal basis for the mouse phenotype but also raises the possibility that G-βγ5 dependent signaling contributes to the pathogenesis of human congenital heart problems.
异源三聚体G蛋白调节许多胚胎发育所必需的过程，包括细胞增殖、迁移、分化和存活。尽管大多数研究集中于确定各种α亚型的作用，但人们越来越认识到，同样具有差异的βγ二聚体也调节这些过程。在本文中，我们表明，靶向破坏编码γ5亚型的小鼠Gng5基因会导致胚胎致死，并伴有严重的头部和心脏缺陷。总体而言，这些结果进一步丰富了越来越多的数据，这些数据表明γ亚基在指导功能不同的G-αβγ三聚体的组装中起关键作用，而这些三聚体负责调节多种生物学过程。具体而言，G-γ5亚型缺失与心脏前体细胞数量减少相关这一发现，不仅为小鼠表型提供了因果依据，也增加了G-βγ5依赖性信号传导导致人类先天性心脏问题发病的可能性。
