FIGURE 3.

Open questions about endocytosis of trypanosomes. The general route of endocytosis and recycling in Trypanosoma brucei is depicted. The gray arrows represent the direction of all cargo while the red arrows refer solely to fluid-phase cargo. Endo- and exocytosis is restricted to a single site in trypanosomes: the flagellar pocket. Thus, the first intriguing question is how does the cell discriminate between cargo entering and leaving the pocket? All molecules are endocytosed via clathrin mediated endocytosis (CME), the recycling rates are incredibly fast, and T. brucei lacks AP-2 (Grünfelder et al., 2002; Morgan et al., 2002; Engstler et al., 2004). Therefore, the naturally following questions are: how fast is CME and does the lack of AP-2 influence this process? VSGs have never been observed in the lysosome and the route to this organelle is likely to be mediated by class II clathrin-coated vesicles (CCV II). So, the remaining questions here are how VSG is excluded from CCV II sorting and how these vesicles are routed to the lysosome. Furthermore, the number of endosomes in T. brucei cells and the origin of exocytic carriers remain elusive as does the mechanism of excretion of 95% of the cargo. Overall, the essentiality of the VSG coat for trypanosomes allied to the natural increase of volume of the cell during the cell cycle advocates for a precise regulatory mechanism to maintain the dense surface coat. However, such a mechanism has not yet been elucidated.