Regulation of VEGF signaling by membrane traffic.
Regulation of VEGF signaling by membrane traffic.
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通过膜流量调节VEGF信号。
DOI：
10.1016/j.cellsig.2012.05.007
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发表时间：
2012-09
影响因子：
4.8
通讯作者：
Seerapu HR
中科院分区：
文献类型：
--
作者：
Horowitz A;Seerapu HR
最近的研究结果引起了人们对膜交通在血管内皮生长因子（VEGF）信号传导中的作用的关注。这一进展的意义源于VEGF在血管生成和血管生成中的关键功能。血管内皮生长因子受体（VEGF receptor， VEGFR）信号通过膜交通调控的大致思路与表皮生长因子受体（epidermal growth factor receptor， EGFR）的调控思路相似，是膜交通与信号相互交织的一个原型。然而，在VEGFR信号中有一些独特的特征，部分是由共受体神经肽（Nrp）的参与赋予的。Nrp1和VEGFR2通过接头蛋白连接蛋白整合到膜运输中，连接蛋白会招募肌凝蛋白VI，这是一种驱动向内运输的分子马达。最近在表达Nrp1缺乏细胞质结构域的敲入小鼠模型中仅检测到轻微的血管缺陷，质疑该共受体在VEGF信号传导和膜运输中的作用。ephrin-B2对内吞作用的调节是VEGR2/3独有的另一个特征，但其机制尚待解释。目前的模型并不能完全解释膜交通如何在VEGFR和产生其功能结果（如细胞迁移）的下游效应物之间架起桥梁。VEGF-A似乎部分通过招募携带RhoA的内吞囊泡来内化活性VEGFR2来完成这一任务。
Recent findings have drawn attention to the role of membrane traffic in the signaling of vascular endothelial growth factor (VEGF). The significance of this development stems from the pivotal function of VEGF in vasculogenesis and angiogenesis. The outline of the regulation of VEGF receptor (VEGFR) signaling by membrane traffic is similar to that of the epidermal growth factor receptor (EGFR), a prototype of the intertwining between membrane traffic and signaling. There are, however, unique features in VEGFR signaling that are conferred in part by the involvement of the co-receptor neuropilin (Nrp). Nrp1 and VEGFR2 are integrated into membrane traffic through the adaptor protein synectin, which recruits myosin VI, a molecular motor that drives inward trafficking. The recent detection of only mild vascular defects in a knockin mouse model that expresses Nrp1 lacking a cytoplasmic domain, questions the co-receptor’s role in VEGF signaling and membrane traffic. The regulation of endocytosis by ephrin-B2 is another feature unique to VEGR2/3, but it awaits a mechanistic explanation. Current models do not fully explain how membrane traffic bridges between VEGFR and the downstream effectors that produce its functional outcome, such as cell migration. VEGF-A appears to accomplish this task in part by recruiting endocytic vesicles carrying RhoA to internalized active VEGFR2.