Spatio-temporal Rho GTPase signaling - where are we now?
Spatio-temporal Rho GTPase signaling - where are we now?
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DOI：
10.1242/jcs.064345
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发表时间：
2010-06-01
影响因子：
4
通讯作者：
Pertz, Olivier
中科院分区：
文献类型：
--
作者：
Pertz, Olivier
rho家族gtpase是将细胞外信号传递到细胞内信号通路的分子开关。它们的调控很可能在空间和时间上受到高度调控，但大多数关于rho家族GTPase信号传导的已知信息都来自于不能解决这些维度的技术。新的成像技术现在允许以高时空分辨率可视化Rho GTPase信号。这导致了深刻的见解，大大扩展了经典模型，并要求一个新的概念框架。这些方法清楚地表明了三件事。首先，Rho GTPase信号动力学发生在微米长度尺度和亚分钟时间尺度上。其次，一个给定Rho GTPase的多个亚细胞池可以在时间和空间上同时起作用，以调节各种形态发生事件（如前缘膜突出、尾回缩、膜皱折）。这些不同的Rho GTPase亚细胞池可以被描述为“时空信号模块”，可能涉及一个GTPase与不同的鸟嘌呤核苷酸交换因子（gef）、gtase激活蛋白（gap）和效应物的特定相互作用。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。下一个挑战是破译这种复杂的时空模块化背后的分子电路，以产生Rho GTPase信号的集成模型。
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.