Sialic acid linkage in glycosphingolipids is a molecular correlate for trafficking and delivery of extracellular cargo.
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.
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.
Madhu Sudhan
MS
Ravindran
Lukas Bahati
LB
Tanner
Markus R
MR
Wenk
D000818:Animals; D001427:Bacterial Toxins / Q000145:classification / Q000378:metabolism; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism / Q000821:virology; D004705:Endocytosis; D011992:Endosomes / Q000378:metabolism / Q000821:virology; D006028:Glycosphingolipids / Q000737:chemistry / Q000145:classification / Q000378:metabolism*; D054884:Host-Pathogen Interactions; D006801:Humans; D019158:N-Acetylneuraminic Acid / Q000737:chemistry* / Q000378:metabolism; D021381:Protein Transport; D014780:Viruses / Q000145:classification / Q000378:metabolism
D001427:Bacterial Toxins; D006028:Glycosphingolipids; D019158:N-Acetylneuraminic Acid
gangliosides; glycosphingolipids; sialic acids; sialidases; toxins; trafficking; viruses