AAGAB Controls AP2 Adaptor Assembly in Clathrin-Mediated Endocytosis
AAGAB Controls AP2 Adaptor Assembly in Clathrin-Mediated Endocytosis
复制标题
AAGAB 在网格蛋白介导的内吞作用中控制 AP2 接头组装
DOI：
10.1016/j.devcel.2019.06.013
复制
发表时间：
2019-08-19
影响因子：
11.8
通讯作者：
Shen, Jingshi
中科院分区：
文献类型：
--
作者：
Gulbranson, Daniel R.;Crisman, Lauren;Shen, Jingshi
多聚体适配器广泛参与囊泡介导的膜转运。尤其是AP2接头，通过募集Cargo和Clathrin到胞内位置，在分子筛介导的胞吞作用(CME)中起着核心作用。通常认为，AP2接头等运输接头是自发组装的。然而，在这项工作中，我们发现AP2接头组装是一个由α和伽马适配素结合蛋白(AAGAB)控制的有序过程，AAGAB是我们在CME全基因组遗传筛查中发现的一个未知因子。AAGAB引导AP2亚基的顺序结合，稳定组装中间体。在没有AAGAB辅助的情况下，AP2亚基不能形成接头复合体，导致其降解。AAGAB的功能被一种突变所废除，该突变导致人类皮肤病-1型点状掌足角化症(PPKP1)。由于其他多MERIC运输接头以类似于AP2接头的方式工作，它们的组装可能涉及类似的调节机制。
Multimeric adaptors are broadly involved in vesicle-mediated membrane trafficking. AP2 adaptor, in particular, plays a central role in clathrin-mediated endocytosis (CME) by recruiting cargo and clathrin to endocytic sites. It is generally thought that trafficking adaptors such as AP2 adaptor assemble spontaneously. In this work, however, we discovered that AP2 adaptor assembly is an ordered process controlled by alpha and gamma adaptin binding protein (AAGAB), an uncharacterized factor identified in our genome-wide genetic screen of CME. AAGAB guides the sequential association of AP2 subunits and stabilizes assembly intermediates. Without the assistance of AAGAB, AP2 subunits fail to form the adaptor complex, leading to their degradation. The function of AAGAB is abrogated by a mutation that causes punctate palmoplantar keratoderma type 1 (PPKP1), a human skin disease. Since other multi-meric trafficking adaptors operate in an analogous manner to AP2 adaptor, their assembly likely involves a similar regulatory mechanism.