Ma Zhuo, Islam Md Nur, Xu Tao, Song Eli
National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
University of Chinese Academy of Sciences, Beijing 100049, China.
Biophys Rep. 2021 Apr 30;7(2):91-100. doi: 10.52601/bpr.2021.200051.
The transport of cargo proteins to specific subcellular destinations is crucial for the different secretory and endocytic traffic pathways. One of the most important steps in maintaining the accuracy of this process is the recruitment of adaptor protein (AP) complexes to the membrane for recognizing and packaging cargo proteins into nascent vesicles. Adaptor protein complex 3 (AP-3) is a heterotetrametric complex implicated in the trafficking of cargo proteins from the trans-Golgi network (TGN) and/or endosomes to lysosomes or lysosome-related organelles (LROs). This complex is also involved in the biogenesis of synaptic vesicles (SVs) in neurons and of dense core vesicles (DCVs) in endocrine cells as well as in the recycling of receptors in immune cells and the regulation of planar cell polarity (PCP) proteins. Functional defects in AP-3 cause multiple abnormalities in cellular vesicle trafficking and related organelle function, leading to various disorders, such as Hermansky-Pudlak syndrome (HPS). However, the molecular mechanism underlying AP-3 has not been fully elucidated, and further investigations are needed to understand AP-3-mediated trafficking, its associated molecules and its related roles in inherited diseases. Here, we review the current understanding of AP-3 in cellular vesicle trafficking, especially focusing on mammalian systems.
货物蛋白运输到特定的亚细胞目的地对于不同的分泌和内吞运输途径至关重要。维持这一过程准确性的最重要步骤之一是将衔接蛋白（AP）复合物募集到膜上，以识别货物蛋白并将其包装到新生囊泡中。衔接蛋白复合物3（AP-3）是一种异源四聚体复合物，参与货物蛋白从反式高尔基体网络（TGN）和/或内体运输到溶酶体或溶酶体相关细胞器（LRO）。该复合物还参与神经元中突触囊泡（SV）和内分泌细胞中致密核心囊泡（DCV）的生物发生，以及免疫细胞中受体的循环和平面细胞极性（PCP）蛋白的调节。AP-3的功能缺陷会导致细胞囊泡运输和相关细胞器功能出现多种异常，从而引发各种疾病，如Hermansky-Pudlak综合征（HPS）。然而，AP-3的分子机制尚未完全阐明，需要进一步研究以了解AP-3介导的运输、其相关分子及其在遗传性疾病中的相关作用。在此，我们综述了目前对AP-3在细胞囊泡运输中的理解，尤其侧重于哺乳动物系统。
