To the Surface and Back: Exo- and Endocytic Pathways in Trypanosoma brucei

Trypanosoma brucei is one of only a few unicellular pathogens that thrives extracellularly in the vertebrate host. Consequently, the cell surface plays a critical role in both immune recognition and immune evasion. The variant surface glycoprotein (VSG) coats the entire surface of the parasite and acts as a flexible shield to protect invariant proteins against immune recognition. Antigenic variation of the VSG coat is the major virulence mechanism of trypanosomes. In addition, incessant motility of the parasite contributes to its immune evasion, as the resulting fluid flow on the cell surface drags immunocomplexes toward the flagellar pocket, where they are internalized. The flagellar pocket is the sole site of endo- and exocytosis in this organism. After internalization, VSG is rapidly recycled back to the surface, whereas host antibodies are thought to be transported to the lysosome for degradation. For this essential step to work, effective machineries for both sorting and recycling of VSGs must have evolved in trypanosomes. Our understanding of the mechanisms behind VSG recycling and VSG secretion, is by far not complete. This review provides an overview of the trypanosome secretory and endosomal pathways. Longstanding questions are pinpointed that, with the advent of novel technologies, might be answered in the near future.

Automated summary

Trypanosoma brucei is a unicellular pathogen that thrives extracellularly in vertebrate hosts, with its cell surface playing a critical role in both immune recognition and evasion. The variant surface glycoprotein (VSG) and incessant motility contribute to immune evasion, while endo- and exocytosis occur at the flagellar pocket. Mechanisms behind VSG recycling and secretion are not fully understood, presenting longstanding questions that may be answered with novel technologies in the future.