Figure 6.

Schematic illustration of proposed mechanism of action of Vacq1-induced endolysosomal disruption and glioblastoma cell death. Vacq1 initiates plasma membrane blebs and ruffles and this activity leads to macropinocytic endocytosis. The newly formed vesicles have two distinct destinations. One pool is fused with lysosomes forming enlarged vacuoles. Vacq1 directly interacts and interferes with CaM. The inhibition of CaM prevents lysosomal reformation from the vacuoles, and consequently enlarged vacuoles accumulate. Within endosomes, Vacq1 activates v-ATPase which causes an abnormal acidification and formation of AVOs. Protonation and trapping of Vacq1 within the lumen of the acidic organelles contributes to glioblastoma cytotoxicity.