Divergent modes for cargo-mediated control of clathrin-coated pit dynamics.
Divergent modes for cargo-mediated control of clathrin-coated pit dynamics.
复制标题
网格蛋白包被的坑动力学的货物介导控制的不同模式。
DOI：
10.1091/mbc.e12-07-0550
复制
发表时间：
2013
影响因子：
3.3
通讯作者：
Puthenveedu,ManojkumarA
中科院分区：
文献类型：
--
作者：
Soohoo,AmandaL;Puthenveedu,ManojkumarA
网格蛋白介导的内吞作用一直被认为是由核心内吞蛋白驱动的过程，其中内化的货物蛋白是被动的。与此相反，一个新兴的观点表明，信号受体货物可能会积极控制其命运，通过调节网格蛋白包被的坑（CCP），介导其内化的动态。尽管它的生理意义，很少有人知道这样的“货物介导的调节”的CCP信号受体。在这里，使用全内反射荧光显微镜成像和定量分析活细胞，我们表明，μ-阿片受体，生理相关的G蛋白偶联信号受体，延迟的CCP的动力学，它是本地化。这种延迟是由受体胞质尾区上两个关键亮氨酸的相互作用介导的。与先前已知的货物介导的调节机制不同，这些残基调节发动蛋白的寿命，发动蛋白是CCP断裂的关键组分。这些结果确定了一种新的手段，用于选择性地控制不同的货物，共享共同的运输组件的内吞作用，并表明CCP调节信号受体可以通过不同的模式。
Clathrin-mediated endocytosis has long been viewed as a process driven by core endocytic proteins, with internalized cargo proteins being passive. In contrast, an emerging view suggests that signaling receptor cargo may actively control its fate by regulating the dynamics of clathrin-coated pits (CCPs) that mediate their internalization. Despite its physiological implications, very little is known about such “cargo-mediated regulation” of CCPs by signaling receptors. Here, using multicolor total internal reflection fluorescence microscopy imaging and quantitative analysis in live cells, we show that the μ-opioid receptor, a physiologically relevant G protein–coupled signaling receptor, delays the dynamics of CCPs in which it is localized. This delay is mediated by the interactions of two critical leucines on the receptor cytoplasmic tail. Unlike the previously known mechanism of cargo-mediated regulation, these residues regulate the lifetimes of dynamin, a key component of CCP scission. These results identify a novel means for selectively controlling the endocytosis of distinct cargo that share common trafficking components and indicate that CCP regulation by signaling receptors can operate via divergent modes.