FIGURE 1: Speculations on the interactions between TLF, APOL1 and CATL, and a possible role for the putative channel protein, Tb927.8.5240.

TLF1 is known to enter T. b. brucei via HpHbR at the flagellar pocket membrane, and then transit to the lysosome where the lytic component, APOL1, forms pores in the lysosomal membrane leading to osmotic swelling and parasite lysis. The mechanism for TLF2 entry is unknown, though it has been speculated that it may interact with surface VSG, which is rapidly endocytosed. The putative channel protein, Tb927.8.5240, represents a possible alternative uptake mechanism; however, the localisation detailed above is speculative. It is unknown whether or where within the endocytic network APOL1 dissociates from TLF. CATL is presumed to act upon either the lytic complexes or APOL1 in the lysosome, as its activity is dependent upon the acidic pH found in this organelle. Reduced human serum sensitivity is due to ‘loss-of-function’ (Green) or ‘gain-of-function’ (Blue); the latter includes SRA and TgsGP, which have been omitted for clarity (see main text for details).