Members of the CIP4 family of proteins participate in the regulation of platelet-derived growth factor receptor-β-dependent actin reorganization and migration
Members of the CIP4 family of proteins participate in the regulation of platelet-derived growth factor receptor-β-dependent actin reorganization and migration
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DOI：
10.1042/bc20090033
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发表时间：
2010-04-01
影响因子：
2.7
通讯作者：
Aspenstrom, Pontus
中科院分区：
文献类型：
--
作者：
Toguchi, Marcia;Richnau, Ninna;Aspenstrom, Pontus
背景信息。 F-BAR {Fes/CIP4 [Cdc42（细胞分裂周期 42）相互作用蛋白 4] 同源性和 BAR (Bin/amphiphyn/Rvs)} 蛋白已成为调节肌动蛋白组装和膜动力学的信号通路的重要协调子。 F-BAR 结构域的存在是该蛋白家族的标志，CIP4（Cdc42 相互作用蛋白 4）是最早鉴定的脊椎动物 F-BAR 蛋白之一。存在三种人类 CIP4 旁系同源物，即 CIP4、FBP17（福尔马林结合蛋白 17）和 Toca-1（Cdc42 依赖性肌动蛋白组装转导子 1）。 CIP4 样蛋白参与 Cdc42 依赖性肌动蛋白重组和脂质双层管状膜变形事件的调节。结果。我们对三个 CIP4 旁系同源物进行了并行分析。我们发现三种 CIP4 样蛋白催化膜管和肌动蛋白重组的有效性各不相同。此外，我们还发现，在激活的 Cdc42 存在下，CIP4 依赖性膜管作用得到增强。一些 F-BAR 成员已被证明在 EGF（表皮生长因子）受体的内吞作用中发挥作用，这促使我们研究 CIP4 样蛋白在 PDGFR beta [PDGF（血小板源性生长因子）β 受体]信号传导中的参与。我们发现 CIP4 样蛋白的敲低导致 PDGF 诱导的背侧皱褶形成时间延长，以及 PDGF 依赖性细胞迁移增加。这很可能是用针对 CIP4 样蛋白的 siRNA（小干扰 RNA）处理的细胞中受体延迟内化引起的持续 PDGFR β 激活的结果。结论。我们的研究结果表明，CIP4 样蛋白诱导 Cdc42 下游的膜管化，并且它们通过调节 PDGFR β 的内化和活性，在 PDGF 依赖性肌动蛋白重组和细胞迁移中发挥重要作用。此外，结果表明 CIP4 样蛋白在调节 PDGFR β 活性中发挥重要作用。
Background information. The F-BAR {Fes/CIP4 [Cdc42 (cell division cycle 42)-interacting protein 4] homology and BAR (Bin/amphiphysin/Rvs)} proteins have emerged as important co-ordinators of signalling pathways that regulate actin assembly and membrane dynamics. The presence of the F-BAR domain is the hallmark of this family of proteins and the CIP4 (Cdc42-interacting protein 4) was one of the first identified vertebrate F-BAR proteins. There are three human CIP4 paralogues, namely CIP4, FBP17 (formin-binding protein 17) and Toca-1 (transducer of Cdc42-dependent actin assembly 1). The CIP4-like proteins have been implicated in Cdc42-dependent actin reorganization and in regulation of membrane deformation events visible as tubulation of lipid bilayers.Results. We performed side-by-side analyses of the three CIP4 paralogues. We found that the three CIP4-like proteins vary in their effectiveness to catalyse membrane tubulation and actin reorganization. Moreover, we show that the CIP4-dependent membrane tubulation is enhanced in the presence of activated Cdc42. Some F-BAR members have been shown to have a role in the endocytosis of the EGF (epidermal growth factor) receptor and this prompted us to study the involvement of the CIP4-like proteins in signalling of the PDGFR beta [PDGF (platelet-derived growth factor) beta-receptor]. We found that knock-down of CIP4-like proteins resulted in a prolonged formation of PDGF-induced dorsal ruffles, as well as an increased PDGF-dependent cell migration. This was most likely a consequence of a sustained PDGFR beta activation caused by delayed internalization of the receptor in the cells treated with siRNA (small interfering RNA) specific for the CIP4-like proteins.Conclusions. Our findings show that CIP4-like proteins induced membrane tubulation downstream of Cdc42 and that they have important roles in PDGF-dependent actin reorganization and cell migration by regulating internalization and activity of the PDGFR beta. Moreover, the results suggest an important role for the CIP4-like proteins in the regulation of the activity of the PDGFR beta.