Figure 7.

A proposed model of Rab35 functional cascades in PODXL trafficking under 2D and 3D culture conditions. Rab35 activation during PODXL trafficking is regulated by distinct Rab35–GEF proteins, depending on the culture conditions (i.e. DENND1A in 3D and FLCN in 2D culture conditions, respectively). DENND1A activates Rab35 and enables it to recruit a Rab35 effector, ACAP2 (Arf6-GAP), in 3D cell cultures. On the other hand, FLCN activates Rab35 and enables it to recruit another Rab35 effector, OCRL (phosphatidylinositol 4,5-bisphosphate phosphatase), in 2D cell cultures, followed by PODXL apical trafficking (6).