Cargo regulates clathrin-coated pit dynamics
Cargo regulates clathrin-coated pit dynamics
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DOI：
10.1016/j.cell.2006.08.035
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发表时间：
2006-10-06
期刊：
影响因子：
64.5
通讯作者：
von Zastrow, Mark
中科院分区：
文献类型：
--
作者：
Puthenveedu, Manojkumar A.;von Zastrow, Mark
笼状蛋白包被小孔(CCP)通常被认为是含有混合的构成和受调控的膜货物的内吞机器的统一群体。与这一观点相反，我们表明G蛋白偶联受体(GPCRs)的调节内吞作用优先通过CCP的一个子集发生。值得注意的是，含有GPCR的CCP在功能上也是不同的，因为它们的表面停留时间是由GPCRCargo通过PDZ依赖的连接到肌动蛋白细胞骨架来局部调节的。这种货物调节的CCP表现出动力蛋白的延迟招募，并可能经历一种流产事件，在这种情况下，网状蛋白涂层从质膜上分离出来，而没有伴随的受体内吞。将货物分成CCP亚集，结合对CCP动态的货物依赖控制，表明了一种简单的动力学机制，可以在内吞途径早期产生功能专门化，减少不同内吞货物之间的竞争。
Clathrin-coated pits (CCPs) are generally considered a uniform population of endocytic machines containing mixed constitutive and regulated membrane cargo. Contrary to this view, we show that regulated endocytosis of G protein-coupled receptors (GPCRs) occurs preferentially through a subset of CCPs. Significantly, GPCR-containing CCPs are also functionally distinct, as their surface residence time is regulated locally by GPCR cargo via PDZ-dependent linkage to the actin cytoskeleton. Such cargo-regulated CCPs show delayed recruitment of dynamin and can undergo an abortive event in which clathrin coats separate from the plasma membrane without concomitant receptor endocytosis. Segregation of cargo into CCP subsets, combined with cargo-dependent control of CCP dynamics, suggests a simple kinetic mechanism to generate functional specialization early in the endocytic pathway and reduce competition between diverse endocytic cargo.