Zuse Institute Berlin, Takustraße 7, 14195 Berlin, Germany.
Department of Mathematics and Computer Science, Free University Berlin, Arnimallee 14, 14195 Berlin, Germany.
Cells. 2022 May 17;11(10):1660. doi: 10.3390/cells11101660.
Spatiotemporal signal shaping in G protein-coupled receptor (GPCR) signaling is now a well-established and accepted notion to explain how signaling specificity can be achieved by a superfamily sharing only a handful of downstream second messengers. Dozens of Gs-coupled GPCR signals ultimately converge on the production of cAMP, a ubiquitous second messenger. This idea is almost always framed in terms of local concentrations, the differences in which are maintained by means of spatial separation. However, given the dynamic nature of the reaction-diffusion processes at hand, the dynamics, in particular the local diffusional properties of the receptors and their cognate G proteins, are also important. By combining some first principle considerations, simulated data, and experimental data of the receptors diffusing on the membranes of living cells, we offer a short perspective on the modulatory role of local membrane diffusion in regulating GPCR-mediated cell signaling. Our analysis points to a diffusion-limited regime where the effective production rate of activated G protein scales linearly with the receptor-G protein complex's relative diffusion rate and to an interesting role played by the membrane geometry in modulating the efficiency of coupling.
G 蛋白偶联受体（GPCR）信号中的时空信号成形现在是一个被广泛接受的概念，用于解释为什么仅通过少数下游第二信使共享的超家族就能实现信号特异性。数十种 Gs 偶联 GPCR 信号最终都集中在 cAMP 的产生上，cAMP 是一种普遍存在的第二信使。这个概念几乎总是以局部浓度的形式来表示，而局部浓度的差异则通过空间分离来维持。然而，考虑到手边的反应扩散过程的动态性质，动力学，特别是受体和其同源 G 蛋白的局部扩散特性，也很重要。通过结合一些基本原理的考虑、模拟数据和活细胞中受体在膜上扩散的实验数据，我们对局部膜扩散在调节 GPCR 介导的细胞信号中的调节作用提供了一个简短的视角。我们的分析指出了一个扩散限制的状态，其中激活的 G 蛋白的有效产生速率与受体 - G 蛋白复合物的相对扩散速率呈线性关系，以及膜几何形状在调节耦合效率方面的有趣作用。
