Leibniz Institute for Molecular Pharmacology, 13125 Berlin, Germany.
Biol Cell. 2012 Oct;104(10):588-602. doi: 10.1111/boc.201200008. Epub 2012 May 31.
Dynamic flux of membrane between intracellular compartments is a key feature of all eukaryotic cells. Soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) play a crucial role in membrane dynamics by facilitating membrane fusion, for example at synapses where small synaptic vesicles (SVs) undergo activity-regulated neuroexocytosis, followed by the endocytic re-cycling of SV proteins and lipids. Recent work shows that the assembly protein 180 (AP180) N-terminal homology (ANTH) domain containing proteins AP180 and clathrin assembly lymphoid myeloid leukaemia (CALM) not only regulate the assembly of the endocytic machinery but also act as sorters for a subset of SNAREs, the vesicle-associated membrane proteins (VAMPs), most notably VAMP/synaptobrevin 2 at synapses. In this review, we summarise the current state of knowledge about the roles of AP180 and CALM family members in clathrin-dependent membrane traffic, the molecular mechanistic basis for their activities and their potential involvement in human disease.
细胞内隔室之间的膜动态通量是所有真核细胞的一个关键特征。可溶性 N-乙基马来酰亚胺敏感因子附着蛋白受体（SNAREs）通过促进膜融合在膜动态中发挥关键作用，例如在突触处，小突触小泡（SVs）经历活性调节的神经胞吐作用，随后 SV 蛋白和脂质的内吞再循环。最近的工作表明，组装蛋白 180（AP180）N 端同源（ANTH）结构域包含蛋白 AP180 和网格蛋白组装淋巴髓性白血病（CALM）不仅调节内吞机制的组装，而且作为一小部分 SNARE 的分拣器，囊泡相关膜蛋白（VAMPs），特别是突触处的 VAMP/synaptobrevin 2。在这篇综述中，我们总结了目前关于 AP180 和 CALM 家族成员在网格蛋白依赖性膜运输中的作用、它们活性的分子机制基础以及它们在人类疾病中的潜在参与的知识状态。
