What would happen if the pH of the late endosome were increased to 6.6?
Dissociation of lysosomal enzymes from mannose-6-phosphate receptors relies on progressive acidification along endocytic pathway driven by V-ATPase multisubunit rotary pump. In trans-Golgi network pH near 6.7 binding between M6P monoester and receptor pocket containing arginine histidine is high affinity nanomolar permitting packaging into vesicles. Upon arrival in late endosomes pH drops via pumping to 5.5-6.0 protonating histidines reducing electrostatic complementarity affinity over hundredfold causing cargo release into lumen while receptors remain membrane bound for retromer VPS26-29-35 r
Ref: Lodish et al., MCB: Acidic late endosome releases M6P enzymes from receptors for lysosome delivery.
