Forword. Regulation of RhoGTPases in motility: A fine balancing act.
Forword. Regulation of RhoGTPases in motility: A fine balancing act.
复制标题
前言。
DOI：
10.1080/19336918.2014.1000242
复制
发表时间：
2014
影响因子：
3.2
通讯作者：
Hodgson,Louis
中科院分区：
文献类型：
--
作者：
Hodgson,Louis
细胞迁移在生理条件下如在发育、免疫应答、伤口愈合和维持组织稳态中是至关重要的。这些过程在病理条件下异常失调，因此，细胞迁移的调节改变导致许多人类疾病，包括发育缺陷、炎性疾病和恶性癌症。细胞运动和迁移的关键组成部分之一是驱动细胞运动的细胞肌动蛋白机制。近年来，小GTP结合蛋白（GTbinding Proteins，GTbinding Proteins）Rho家族的调控机制逐渐被阐明，其调控机制主要受上游调控因子鸟嘌呤核苷酸交换因子（Guanine-nucleotide Exchange Factors，GEF）、GTbinding Activating Proteins（GAP）和鸟嘌呤核苷酸解离抑制因子（Guanine-nucleotide Dissociation Inhibitor，GDI）的平衡调节。信号调节和转导的特异性严重依赖于正确的空间和时间线索的整合，这些线索决定了亚细胞尺度内的RhoGTdR激活状态和秒级的时间分辨率。在这个特殊的部分中，我们专注于RhoGT 3信号传导领域的现状，并从RhoGT 3亚型特异性和上游GEF特异性的角度出发，部分驱动基于肌动蛋白的运动机制的整体，最终协调细胞迁移行为，与细胞肌动蛋白细胞骨架调节和运动性经典相关的RhoGTP酶是RhoA、Rac 1和Cdc 42。然而，存在共享高达90+%的一级氨基酸序列但由不同基因产物产生的相近同种型，并且它们似乎调节与经典RhoGTP酶非常不同的功能。RhoGTPases的这些亚型在不同细胞类型中的表达谱似乎表明在许多尚未完全阐明的疾病特异性情况下的不同作用。在这里，Donnelly等人1回顾了RhoGTdR的这些方面。
Cell migration is vitally important under physiological conditions such as in development, immune response, wound healing and in maintenance of the tissue homeostasis. These processes are aberrantly dysregulated in pathologic conditions and thus, altered regulation of cell migration results in many human diseases including developmental defects, inflammatory diseases and malignant cancers. One of the critical components of cell motility and migration is the cellular actin machinery that drives the cell locomotion. In recent years, regulatory mechanisms are being elucidated that involve Rho family of small GTP-binding proteins (GTPase), regulated by the balance of their upstream regulators Guanine-nucleotide Exchange Factors (GEF), GTPase Activating Proteins (GAPs) and the Guanine-nucleotide Dissociation Inhibitor (GDI). The specificity of signal regulation and transduction is critically dependent on the integration of correct spatial and temporal cues that dictate the RhoGTPase activation status within subcellular scales and time resolution in the order of seconds. In this special section, we focus on the current state of the field in RhoGTPase signaling, and approach it from the stand point of RhoGTPase isoform specificity and the upstream GEF-specificity that, in part, drive the ensemble of actin-based motility machinery, ultimately orchestrating the coordinated cellular migratory behaviors, both under normal and pathologic conditions.RhoGTPases classically associated with cellular actin cytoskeleton regulation and motility are RhoA, Rac1 and Cdc42. However, close isoforms that share up to 90+% primary amino acid sequence but arise from separate gene products exist, and they appear to regulate very different functions from the classical RhoGTPases. The expression profiles of these isoforms of RhoGTPases in different cell types appear to suggest differential roles in many disease-specific situations that are not yet fully elucidated. Here, Donnelly et al. 1 reviews these aspects of RhoGTPase