Clathrin-independent endocytosis used by the IL-2 receptor is regulated by Rac1, Pak1 and Pak2
Clathrin-independent endocytosis used by the IL-2 receptor is regulated by Rac1, Pak1 and Pak2
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DOI：
10.1038/embor.2008.28
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发表时间：
2008-04-01
期刊：
影响因子：
7.7
通讯作者：
Sauvonnet, Nathalie
中科院分区：
文献类型：
--
作者：
Grassart, Alexandre;Dujeancourt, Annick;Sauvonnet, Nathalie
存在几种内吞途径，其依赖于或不依赖于网格蛋白。这项研究的重点是一个不好的特点机制-网格蛋白-和小窝-独立的内吞作用-所使用的白细胞介素-2受体β（IL-2 R β）。我们解决的问题，它的监管相比，网格蛋白依赖的途径。首先，我们表明Ras相关的C3肉毒杆菌毒素底物1（Rac 1）是IL-2 R β进入所必需的，我们确定p21激活的激酶（Paks）作为下游靶点。通过RNA干扰，我们表明Pak 1和Pak 2都是IL-2 R β摄取所必需的，与网格蛋白依赖性途径相反。我们观察到，corneumn，肌动蛋白和发动蛋白-两个基本的内吞因子-的合作伙伴是必需的IL-2 R β摄取。此外，我们发现，coronin的行为下游的Paks，这表明控制其功能的这些激酶。因此，我们描述了一个级联反应组成的Rac 1，Paks和corneum特异性调节IL-2 R β的内化。这项研究表明Paks是网格蛋白非依赖性内吞途径的第一个特异性调节剂。
There are several endocytic pathways, which are either dependent on or independent of clathrin. This study focuses on a poorly characterized mechanism - clathrin- and caveolae-independent endocytosis - used by the interleukin-2 receptor beta (IL-2R beta). We address the question of its regulation in comparison with the clathrin- dependent pathway. First, we show that Ras-related C3 botulinum toxin substrate 1 ( Rac1) is specifically required for IL-2R beta entry, and we identify p21-activated kinases (Paks) as downstream targets. By RNA interference, we show that Pak1 and Pak2 are both necessary for IL-2R beta uptake, in contrast to the clathrin- dependent route. We observe that cortactin, a partner of actin and dynamin - two essential endocytic factors - is required for IL-2R beta uptake. Furthermore, we find that cortactin acts downstream from Paks, suggesting control of its function by these kinases. Thus, we describe a cascade composed of Rac1, Paks and cortactin specifically regulating IL-2R beta internalization. This study indicates Paks as the first specific regulators of the clathrin- independent endocytosis pathway.