Ravindran Madhu Sudhan, Tanner Lukas Bahati, Wenk Markus R
Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117456, Singapore; NUS Graduate School for Integrative Sciences and Engineering (NGS), National University of Singapore, Singapore, 117456, Singapore; Present address: Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Traffic. 2013 Nov;14(11):1182-91. doi: 10.1111/tra.12100. Epub 2013 Sep 16.
Gangliosides, glycosphingolipids containing sialic acid moieties, are well known mediators of transmembrane signaling and endocytosis at the plasma membrane. However, little is known about their precise regulatory role at the cell periphery for intracellular sorting of extracellular cargo. Here we inspected published scientific literature for two types of cargoes, namely bacterial toxins and viruses, regarding their usage of gangliosides. We derived a rather simple yet surprisingly consistent framework to classify 20 viruses from 12 different families and five type AB bacterial toxins into two broad categories. We propose that gangliosides with terminally attached sialic acids classify cargo for uptake and trafficking early in the endocytic pathway while gangliosides with internally attached sialic acids associate with uptake and trafficking of cargo late in the endocytic system. Our study provides a testable hypothesis for future investigations into a wide range of trafficking events. It could be utilized as a framework for other intracellular pathogens where lipids are known to be involved in recognition and trafficking. For instance, predictions can be put forward and evaluated based on ganglioside binding patterns and intracellular trafficking routes. Finally, incorporation of our classifier into large scale systems-biology studies could help reveal related molecular determinants in subcellular sorting.
神经节苷脂是含有唾液酸部分的糖鞘脂，是质膜上跨膜信号传导和内吞作用的众所周知的介质。然而，关于它们在细胞外周对细胞外货物进行细胞内分选的确切调节作用，人们所知甚少。在这里，我们查阅了已发表的科学文献，研究了两种货物，即细菌毒素和病毒，关于它们对神经节苷脂的利用情况。我们得出了一个相当简单但惊人一致的框架，将来自12个不同科的20种病毒和5种AB型细菌毒素分为两大类。我们提出，末端连接唾液酸的神经节苷脂在早期内吞途径中对货物进行摄取和运输分类，而内部连接唾液酸的神经节苷脂则与晚期内吞系统中货物的摄取和运输相关。我们的研究为未来对广泛的运输事件的研究提供了一个可检验的假设。它可以作为其他已知脂质参与识别和运输的细胞内病原体的框架。例如，可以根据神经节苷脂结合模式和细胞内运输途径提出并评估预测。最后，将我们的分类器纳入大规模系统生物学研究中，可能有助于揭示亚细胞分选中的相关分子决定因素。
