Figure 9.
Schematic depicting the effects of wild-type lrrk and lrrkGS on rab7-dependent lysosome positioning. (A) Via multiple binding partners, Rab7 recruits the dynein–dynactin complex to lysosome membranes, thereby promoting their microtubule minus-end-directed motility. The net result is increased localization and clustering of lysosomes in the perinuclear region. Wild-type lrrk negatively regulates this function of rab7. (B) In contrast, lrrkGS actually promotes rab7-dependent perinuclear lysosome positioning in a microtubule- and dynein-dependent manner, resulting in increased localization and clustering of lysosomes in the perinuclear region.