Institute for Biochemistry and Genetics, Department of Biomedicine, University of Basel, Mattenstrasse 28, 4058 Basel, Switzerland.
J Cell Sci. 2010 Jun 1;123(Pt 11):1841-50. doi: 10.1242/jcs.064345.
Rho-family GTPases are molecular switches that transmit extracellular cues to intracellular signaling pathways. Their regulation is likely to be highly regulated in space and in time, but most of what is known about Rho-family GTPase signaling has been derived from techniques that do not resolve these dimensions. New imaging technologies now allow the visualization of Rho GTPase signaling with high spatio-temporal resolution. This has led to insights that significantly extend classic models and call for a novel conceptual framework. These approaches clearly show three things. First, Rho GTPase signaling dynamics occur on micrometer length scales and subminute timescales. Second, multiple subcellular pools of one given Rho GTPase can operate simultaneously in time and space to regulate a wide variety of morphogenetic events (e.g. leading-edge membrane protrusion, tail retraction, membrane ruffling). These different Rho GTPase subcellular pools might be described as 'spatio-temporal signaling modules' and might involve the specific interaction of one GTPase with different guanine nucleotide exchange factors (GEFs), GTPase-activating proteins (GAPs) and effectors. Third, complex spatio-temporal signaling programs that involve precise crosstalk between multiple Rho GTPase signaling modules regulate specific morphogenetic events. The next challenge is to decipher the molecular circuitry underlying this complex spatio-temporal modularity to produce integrated models of Rho GTPase signaling.
Rho 家族 GTPases 是一种分子开关，可将细胞外信号传递至细胞内信号通路。它们的调控很可能在空间和时间上受到高度调控，但人们对 Rho 家族 GTPase 信号转导的了解大多来自于无法解析这些维度的技术。新的成像技术现在可以实现 Rho GTPase 信号的高时空分辨率可视化。这一发现极大地扩展了经典模型，并需要一种新的概念框架。这些方法清楚地表明了三件事。首先，Rho GTPase 信号转导动力学发生在微米长度尺度和亚分钟时间尺度上。其次，给定 Rho GTPase 的多个亚细胞池可以同时在时间和空间上运作，以调节多种形态发生事件（例如前沿膜突起、尾部回缩、膜皱襞）。这些不同的 Rho GTPase 亚细胞池可以被描述为“时空信号模块”，并可能涉及一种 GTPase 与不同的鸟嘌呤核苷酸交换因子（GEF）、GTPase 激活蛋白（GAP）和效应物的特异性相互作用。第三，涉及多个 Rho GTPase 信号模块之间精确串扰的复杂时空信号程序调节特定的形态发生事件。下一个挑战是解析这种复杂时空模块化的分子电路，以产生 Rho GTPase 信号的综合模型。
