Regulation of circular dorsal ruffles, macropinocytosis, and cell migration by RhoG and its exchange factor, Trio.
Regulation of circular dorsal ruffles, macropinocytosis, and cell migration by RhoG and its exchange factor, Trio.
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DOI：
10.1091/mbc.e16-06-0412
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发表时间：
2017-07-01
影响因子：
3.3
通讯作者：
Garcia-Mata R
中科院分区：
文献类型：
--
作者：
Valdivia A;Goicoechea SM;Awadia S;Zinn A;Garcia-Mata R
小GTPase RhoG及其交换因子Trio调节圆形背褶的形成和大小以及相关功能，包括巨噬细胞和细胞迁移。圆形背褶（CDRs）是一种富含肌动蛋白的结构，在许多哺乳动物细胞的背表面形成，是对生长因子刺激的反应。cdr代表了一种独特的结构类型，它在刺激后短暂形成，只形成一次。cdr的形成涉及细胞骨架的剧烈重排，这是由GTPases的Rho家族调节的。到目前为止，只有Rac1与CDR的形成一致，而其他gtpase在这一过程中的作用要么缺乏，要么不确定。在这里，我们表明RhoG及其交换因子Trio在CDR动力学的调节中发挥作用，特别是通过调节它们的大小。RhoG被PDGF下游的Trio以PI3K和src依赖的方式激活。沉默RhoG表达会减少形成cdr的细胞数量，以及cdr的面积。RhoG对CDR区的调控是独立于Rac1功能的。此外，我们的研究结果表明，RhoG在与CDR形成相关的细胞功能中发挥作用，包括巨噬细胞作用、受体内化和细胞迁移。综上所述，我们的研究结果揭示了RhoG在调节cdr及其形成相关的细胞过程中的新作用。
The small GTPase RhoG and its exchange factor, Trio, regulate the formation and size of circular dorsal ruffles and associated functions, including macropinocytosis and cell migration. Circular dorsal ruffles (CDRs) are actin-rich structures that form on the dorsal surface of many mammalian cells in response to growth factor stimulation. CDRs represent a unique type of structure that forms transiently and only once upon stimulation. The formation of CDRs involves a drastic rearrangement of the cytoskeleton, which is regulated by the Rho family of GTPases. So far, only Rac1 has been consistently associated with CDR formation, whereas the role of other GTPases in this process is either lacking or inconclusive. Here we show that RhoG and its exchange factor, Trio, play a role in the regulation of CDR dynamics, particularly by modulating their size. RhoG is activated by Trio downstream of PDGF in a PI3K- and Src-dependent manner. Silencing RhoG expression decreases the number of cells that form CDRs, as well as the area of the CDRs. The regulation of CDR area by RhoG is independent of Rac1 function. In addition, our results show the RhoG plays a role in the cellular functions associated with CDR formation, including macropinocytosis, receptor internalization, and cell migration. Taken together, our results reveal a novel role for RhoG in the regulation of CDRs and the cellular processes associated with their formation.