货物调节网格蛋白包被小窝的动力学。
Cargo regulates clathrin-coated pit dynamics.
作者信息
Puthenveedu Manojkumar A, von Zastrow Mark
机构信息
Department of Psychiatry, University of California at San Francisco, 600 16th Street, San Francisco, CA 94158, USA.
出版信息
Cell. 2006 Oct 6;127(1):113-24. doi: 10.1016/j.cell.2006.08.035.
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.
网格蛋白包被小窝(CCPs)通常被认为是一群均一的内吞机器,包含混合的组成型和调节型膜货物。与这种观点相反,我们发现G蛋白偶联受体(GPCRs)的调节性内吞作用优先通过CCPs的一个亚群发生。值得注意的是,含有GPCR的CCPs在功能上也有所不同,因为它们在表面的停留时间通过GPCR货物经由与肌动蛋白细胞骨架的PDZ依赖性连接而受到局部调节。这种货物调节的CCPs显示发动蛋白的募集延迟,并且可能经历一种异常事件,即网格蛋白包被与质膜分离而没有伴随的受体内吞作用。货物分离到CCP亚群中,再加上货物对CCP动态的依赖性控制,提示了一种简单的动力学机制,可在内吞途径早期产生功能特化并减少不同内吞货物之间的竞争。