Devreotes Peter, Janetopoulos Chris
Department of Cell Biology, Johns Hopkins University, School of Medicine, Baltimore, Maryland 21205, USA.
J Biol Chem. 2003 Jun 6;278(23):20445-8. doi: 10.1074/jbc.R300010200. Epub 2003 Apr 2.
Directional sensing and polarization are fundamental cellular responses that play a central role in health and disease. In this review we define each process and evaluate a series of models previously proposed to explain these phenomena. New findings show that directional sensing by G protein-coupled receptors is localized at a discrete step in the signaling pathway downstream of G protein activation but upstream of the accumulation of PIP3. Local levels of PIP3, whether triggered by chemoattractants, particle binding, or spontaneous events, determine the sites of new actin-filled projections. Robust control of the temporal and spatial levels of PIP3 is achieved by reciprocal regulation of PI3K and PTEN. These observations suggest that a local excitation-global inhibition model can account for the localization of PI3K and PTEN and thereby explain directional sensing. However, elements of other models, including positive feedback and the reaction of the cytoskeleton, must be invoked to account for polarization.
方向感知和极化是基本的细胞反应，在健康和疾病中起着核心作用。在本综述中，我们定义了每个过程，并评估了先前提出的一系列用于解释这些现象的模型。新的研究结果表明，G蛋白偶联受体的方向感知定位在G蛋白激活下游但PIP3积累上游的信号通路中的一个离散步骤。PIP3的局部水平，无论是由趋化因子、颗粒结合还是自发事件触发，都决定了新的充满肌动蛋白的突起的位点。通过PI3K和PTEN的相互调节实现对PIP3时间和空间水平的稳健控制。这些观察结果表明，局部兴奋-全局抑制模型可以解释PI3K和PTEN的定位，从而解释方向感知。然而，必须调用其他模型的要素，包括正反馈和细胞骨架的反应，来解释极化。
