The multiple roles of Rab9 in the endolysosomal system

The small GTPase Rab9 has long been described as a protein that mediates endosome-to-trans-Golgi Network (TGN) transport, and specifically mannose-6-phospate receptor (MPR) recycling. However, studies have challenged this view by showing that Rab9 also is connected to sorting pathways toward the endolysosomal compartments. We recently characterized the spatio-temporal dynamics of Rab9 and, by using live cell imaging, we showed that it enters the endosomal pathway together with CI-MPR at the transition stage between early, Rab5-positive, and late, Rab7a-positive, endosomes. More so, the Rab9 constitutively active mutant, Rab9Q66L, accumulates on late endosomes and promotes carrier formation at the TGN. Here, we discuss our findings in light of previous reports on Rab9 in the retrograde transport pathway.