Figure 8. Proposed ISG65 trafficking pathways.

Schematic diagram of the endocytic pathways of trypanosomes. Black arrows indicate documented routes between the flagellar pocket (FP), early endosome (EE), recycling endosome (RE), late endosome (LE), and the terminal lysosome (Lyso). Dashed arrow indicates uncertain pathway for exocytosis of degraded endocytic cargo (Hall et al., 2005). Validated markers for each compartment are: EE, TbRab5A/B (Pal, Hall, Nesbeth, Field, & Field, 2002); RE, TbRab11 (Jeffries, Morgan, & Field, 2001; Umaer et al., 2018); LE, TbRab7 (Engstler et al., 2004; Silverman et al., 2011), TbRab28 (Lumb et al., 2011), TbVps4 (Silverman et al., 2013), TbVps23 (Leung et al., 2008; Silverman et al., 2013), and TbVps24 (this work); Lyso, p67 (Alexander et al., 2002) and TbCatL (Koeller & Bangs, 2018; Peck et al., 2008). TbFab1 localizes to both LE and Lyso (Gilden et al., 2017). TbVdu1 localizes to the FP/EE region (Zoltner et al., 2015). Spiny coats indicate known sites of clathrin coated vesicle formation (Grunfelder et al., 2003; Morgan, Allen, Jeffries, Hollinshead, & Field, 2001). Points at which RNAi silencing of a given component may block an ISG65 pathway are indicated (red). The point at which TbRME-8 silencing blocks recycling of ISGs, leading to enhanced destruction, is not clear (Koumandou et al., 2013). Knockdown of TbVdu enhances ISG65 turnover (green). Numbers indicate steps referred to in the text.