Remodeling of endosomes during lysosome biogenesis involves 'kiss and run' fusion events regulated by rab5

The small GTPase rab5 has been shown to play key roles in the function of both endocytic and phagocytic organelles. Although these organelles share several additional common features, different processes have been proposed to explain their biogenesis. In the present study, we provide evidence that lysosome biogenesis involves mechanisms similar to those previously described for the formation of phagolysosomes. Transient interactions ('kiss and run') between endocytic organelles are shown to occur during lysosome biogenesis. These interactions are regulated initially by the GTPase activity of rab5, as demonstrated by the loss of size-selective fusion between endosomes in cells expressing a GTPase-deficient mutant of rab5. Endocytic compartments in these cells sequentially display properties of early and late endosomes. However, the formation of lysosomes and the sorting of endocytic solute materials to small electron dense vacuoles are not affected by the rab5 mutation. Together, our results indicate that endosome maturation occurs during the early part of lysosome biogenesis. This process involves transient fusion events regulated, in part, by the small GTPase rab5.