Kutys Matthew L, Yamada Kenneth M
a Laboratory of Cell and Developmental Biology; National Institute of Dental and Craniofacial Research; National Institutes of Health.
Small GTPases. 2015;6(1):16-9. doi: 10.4161/21541248.2014.989792.
Investigating cell migration in 3D settings has revealed that specific extracellular matrix environments require differential activities of the Rho GTPases for efficient migration. However, it is largely unknown how the activities of specific Rho GTPases are modulated to direct cell migration in response to different extracellular matrix cues. We have recently reported that extracellular matrix-dependent regulation of a specific Rho GEF is a fundamental mechanism governing cell migration in different microenvironments, providing a direct mechanism for extracellular matrix-specific regulation of Rho GTPase activity directing cell motility. We discovered that the Rho GEF βPix has a unique function during cell migration in fibrillar collagen environments by restraining RhoA signaling through a conserved signaling axis involving Cdc42 and the Rho GAP srGAP1. In this Commentary, we expand upon this new pathway and discuss potential mechanotransductive and therapeutic applications. Additionally, we speculate on a generalized role for Rho GEFs and GAPs in providing localized, context-dependent responses to the cellular microenvironment during cell migration and other cellular processes.
对三维环境中细胞迁移的研究表明，特定的细胞外基质环境需要Rho GTP酶的不同活性才能实现高效迁移。然而，在很大程度上，人们尚不清楚特定Rho GTP酶的活性是如何被调节，以响应不同的细胞外基质信号来指导细胞迁移的。我们最近报道，特定Rho鸟嘌呤核苷酸交换因子（Rho GEF）的细胞外基质依赖性调节是控制细胞在不同微环境中迁移的一种基本机制，为细胞外基质特异性调节Rho GTP酶活性以指导细胞运动提供了一种直接机制。我们发现，Rho GEF βPix在纤维状胶原环境中的细胞迁移过程中具有独特功能，它通过一个涉及Cdc42和Rho GTP酶激活蛋白（Rho GAP）srGAP1的保守信号轴来抑制RhoA信号传导。在本述评中，我们将扩展这条新途径，并讨论其潜在的机械转导和治疗应用。此外，我们推测Rho GEF和Rho GAP在细胞迁移及其他细胞过程中对细胞微环境提供局部的、依赖于环境的反应方面具有普遍作用。
