Trypanosomes & TLF

We are particularly interested in the transport of the trypanolytic factors (TLFs) from the flagellar pocket to  the lysosome (their point of action), and the proteins and pathways involved in this process. Work by others has shown that TLF1 enters the cell via the TbHpHb receptor, and that ApoL1 (a component of TLF1/2) causes cell lysis by forming pores in the lysosomal membrane, while the expression of the serum resistance antigen renders T. b. rhodesisense resistant to human serum. However, there are significant gaps in our knowledge about this process and the means by which African trypanosomes can become resistant to lysis by human serum. For example, how does TLF2 enter the cell? What components of the cell’s endocytic machinery are responsible for the intracellular transit of TLF to the lysosome? How is the lytic component (ApoL1) released from the TLF particle? What is the molecular basis for T. b. gambiense resistance to TLF/ApoL1? Though changes in the TbHpHb receptor seem to be involved, this isn’t the whole story.