Mammalian membrane trafficking as seen through the lens of bacterial toxins

Abstract

A fundamental question of eukaryotic cell biology is how membrane organelles are organised and interact with each other. Cell biologists address these questions by characterising the structural features of membrane compartments and the mechanisms that coordinate their exchange. To do so, they must rely on variety of cargo molecules and treatments that enable targeted perturbation, localisation, and labelling of specific compartments. In this context, bacterial toxins emerged in cell biology as paradigm shifting molecules that enabled scientists to not only study them from the side of bacterial infection but also from the side of the mammalian host. Their selectivity, potency, and versatility made them exquisite tools for uncovering much of our current understanding of membrane trafficking mechanisms. Here, we will follow the steps that lead toxins until their intracellular targets, highlighting how specific events helped us comprehend membrane trafficking and establish the fundamentals of various cellular organelles and processes. Bacterial toxins will continue to guide us in answering crucial questions in cellular biology while also acting as probes for new technologies and applications.

Keywords: cell membrane; mechanism of action; toxins; trafficking.

Figure 1

Trafficking routes influenced by bacterial toxins as shown for a hypothetical toxin with an active and binding subunit. The plasma membrane, endosome, and retrograde (Golgi to ER) pathways are depicted with their multiple mechanisms to access the cytosol. In addition, processes that were elucidated thanks to toxins are shown in the blue shading. EE, early endosome; ER, endoplasmic reticulum; ESCRT, endosomal sorting complexes required for transport; GSL, glycosphingolipids; ILV, intraluminal vesicle; PM, plasma membrane; SNAREs, soluble NSF‐attachment protein receptors (We thank Giorgia Brambilla Pisoni for her illustration)