Adaptor Autoregulation Promotes Coordinated Binding within Clathrin Coats
Adaptor Autoregulation Promotes Coordinated Binding within Clathrin Coats
复制标题
DOI：
10.1074/jbc.m112.349035
复制
发表时间：
2012-05-18
影响因子：
4.8
通讯作者：
Duncan, Mara C.
中科院分区：
文献类型：
--
作者：
Hung, Chao-Wei;Aoh, Quyen L.;Duncan, Mara C.
膜运输是允许蛋白质和脂质在内吞、溶酶体和分泌区室之间交换的重要过程。网格蛋白介导的跨高尔基体网络和内体之间的交通通过生物合成和内吞蛋白质货物的分选介导对环境的响应。通过该途径的交通是由起始细胞器的胞质表面上的网格蛋白-衔接蛋白外壳的受控组装启动的。在这个过程中，网格蛋白被不同的衔接蛋白募集，这些衔接蛋白充当网格蛋白和待转运的跨膜货物蛋白之间的桥梁。衔接子和网格蛋白之间以及不同类型衔接子之间的相互作用导致在被膜内形成密集的蛋白质网络。一个关键的未解决的问题是如何高度复杂的适配器-网格蛋白相互作用和适配器-适配器相互作用景观导致正确的时空组装的网格蛋白外套。在这里，我们报告发现了一个新的自动调节基序内的网格蛋白适配器Gga 2驱动协同结合Gga 2网格蛋白和适配器Ent 5。这种自动调节影响Gga 2-Ent 5相互作用的时间和/或空间位置。我们建议，这种协同结合提供了内置的调节，以确保正确的组装网格蛋白外套。
Membrane traffic is an essential process that allows protein and lipid exchange between the endocytic, lysosomal, and secretory compartments. Clathrin-mediated traffic between the trans-Golgi network and endosomes mediates responses to the environment through the sorting of biosynthetic and endocytic protein cargo. Traffic through this pathway is initiated by the controlled assembly of a clathrin-adaptor protein coat on the cytosolic surface of the originating organelle. In this process, clathrin is recruited by different adaptor proteins that act as a bridge between clathrin and the transmembrane cargo proteins to be transported. Interactions between adaptors and clathrin and between different types of adaptors lead to the formation of a densely packed protein network within the coat. A key unresolved issue is how the highly complex adaptor-clathrin interaction and adaptor-adaptor interaction landscape lead to the correct spatiotemporal assembly of the clathrin coat. Here we report the discovery of a new autoregulatory motif within the clathrin adaptor Gga2 that drives synergistic binding of Gga2 to clathrin and the adaptor Ent5. This autoregulation influences the temporal and/or spatial location of the Gga2-Ent5 interaction. We propose that this synergistic binding provides built-in regulation to ensure the correct assembly of clathrin coats.