Retrograde transport pathways utilised by viruses and protein toxins

Abstract

A model has been presented for retrograde transport of certain toxins and viruses from the cell surface to the ER that suggests an obligatory interaction with a glycolipid receptor at the cell surface. Here we review studies on the ER trafficking cholera toxin, Shiga and Shiga-like toxins, Pseudomonas exotoxin A and ricin, and compare the retrograde routes followed by these protein toxins to those of the ER trafficking SV40 and polyoma viruses. We conclude that there is in fact no obligatory requirement for a glycolipid receptor, nor even with a protein receptor in a lipid-rich environment. Emerging data suggests instead that there is no common pathway utilised for retrograde transport by all of these pathogens, the choice of route being determined by the particular receptor utilised.

Figure 1

Generalised simplified retrograde routes available to ER trafficking toxins and viruses. Association of the toxin/receptor complex or virus/receptor complex with a receptor in detergent resistant membrane microdomains (DRM) facilitates uptake in caveosomes (C) or transport from early/sorting endosomes (EE/SE) to the TGN, directing a proportion of the toxin or virus away from the late endosome (LE)/lysosome (L) pathway and subsequent destruction. A clear exception is Pseudomonas exotoxin A, which can also utilise a LE to TGN pathway to avoid lysosomal destruction. For toxins, transport from the TGN to the ER may proceed via the Golgi stack or may be direct: for SV40 and Py, ER transport appears to proceed directly from caveosomes.