Fig. 5

The transition from early to late endosomes. Binding and activation of VPS34 on endosomes are initiated through the recruitment of RAB5 to endosomes by the guanine nucleotide exchange factor Rabex5. VPS34 then produces PI3P increasing the binding of RAB5 and other downstream effectors. The transition from early to late endosomes is complicated by a positive feedback loop between Rabex5 and RAB5. MON1A is needed to interrupt this positive feedback loop by displacing Rabex5 from endosomal membranes. MON1A also manages the recruitment of RAB7. VPS34 recruits TBC1D2 protein to endosomes in a RAB7-dependent manner to further inactivate RAB5 and to facilitate early to late endosome maturation