RhoD activated by fibroblast growth factor induces cytoneme-like cellular protrusions through mDia3C.
RhoD activated by fibroblast growth factor induces cytoneme-like cellular protrusions through mDia3C.
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DOI：
10.1091/mbc.e12-04-0315
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发表时间：
2012-12
影响因子：
3.3
通讯作者：
Endo T
中科院分区：
文献类型：
--
作者：
Koizumi K;Takano K;Kaneyasu A;Watanabe-Takano H;Tokuda E;Abe T;Watanabe N;Takenawa T;Endo T
由成纤维细胞生长因子（FGF）信号转导激活的小GTdR h o D通过激活mDia 3C形成基于肌动蛋白的、细胞丝样的、薄且长的细胞突起。这些突起向细胞体传递FGF受体。它们可能负责FGF产生细胞和靶细胞之间的细胞间通讯。小的GTdR RhoD调节肌动蛋白细胞骨架，使肌动蛋白应力纤维和粘着斑塌陷，从而抑制细胞迁移和胞质分裂。它还诱导早期内体沿着肌动蛋白丝排列并降低其运动性。我们在这里表明，组成性激活RhoD产生两种类型的肌动蛋白含有薄的外周细胞突起不同Cdc 42诱导的丝状伪足。一个较长，几乎是直的，不动的，对固定敏感，而另一个较短，起伏，能动的，抵抗固定。此外，表达野生型RhoD的细胞向成纤维细胞生长因子（FGF）2/4/8包被的珠延伸突起。用这些FGF刺激野生型RhoD表达细胞也引起细胞突起的形成。结节移动通过RhoD诱导的较长的突起，主要是对细胞体。外源性表达的FGF受体与这些含有内体样囊泡的移动结节相关。这些结果表明，突起负责FGF及其受体介导的细胞间通讯。因此，突起在形态上和功能上等同于细胞素。RhoD被FGF 2/4/8激活。RhoD的敲除干扰FGF诱导的突起形成。活化的RhoD特异性结合mDia 3C并促进肌动蛋白与mDia 3C一起聚合。mDia 3C定位于突起的尖端或茎部。此外，组成性激活的mDia 3C形成突起，而没有RhoD或FGF刺激。mDia 3的敲低阻碍RhoD诱导的突起形成。这些结果表明，通过FGF信号激活的RhoD通过激活mDia 3C形成细胞丝样突起，这诱导肌动蛋白丝形成。
The small GTPase RhoD, activated by fibroblast growth factor (FGF) signaling, forms actin-based, cytoneme-like, thin and long cellular protrusions through activating mDia3C. These protrusions transmit FGF receptors toward the cell body. They are likely to be responsible for intercellular communication between FGF-producing cells and target cells. The small GTPase RhoD regulates actin cytoskeleton to collapse actin stress fibers and focal adhesions, resulting in suppression of cell migration and cytokinesis. It also induces alignment of early endosomes along actin filaments and reduces their motility. We show here that a constitutively activated RhoD generated two types of actin-containing thin peripheral cellular protrusions distinct from Cdc42-induced filopodia. One was longer, almost straight, immotile, and sensitive to fixation, whereas the other was shorter, undulating, motile, and resistant to fixation. Moreover, cells expressing wild-type RhoD extended protrusions toward fibroblast growth factor (FGF) 2/4/8–coated beads. Stimulation of wild-type RhoD-expressing cells with these FGFs also caused formation of cellular protrusions. Nodules moved through the RhoD-induced longer protrusions, mainly toward the cell body. Exogenously expressed FGF receptor was associated with these moving nodules containing endosome-like vesicles. These results suggest that the protrusions are responsible for intercellular communication mediated by FGF and its receptor. Accordingly, the protrusions are morphologically and functionally equivalent to cytonemes. RhoD was activated by FGF2/4/8. Knockdown of RhoD interfered with FGF-induced protrusion formation. Activated RhoD specifically bound to mDia3C and facilitated actin polymerization together with mDia3C. mDia3C was localized to the tips or stems of the protrusions. In addition, constitutively activated mDia3C formed protrusions without RhoD or FGF stimulation. Knockdown of mDia3 obstructed RhoD-induced protrusion formation. These results imply that RhoD activated by FGF signaling forms cytoneme-like protrusions through activation of mDia3C, which induces actin filament formation.