Endosomal proteolysis of internalized proteins

Endosomal proteases have been implicated in the degradation of internalized regulatory peptides involved in the control of metabolic pathways and in the processing of intracellular antigens for cytolytic immune responses. Processing in the endocytic vesicles is regulated by changes in endosomal acidity due to the presence of an ATP-dependent proton pump which modulates protease activity, protein unfolding and receptor-ligand interactions, A limited number of proteases appear to reside in endosomes which do not contain the full complement of active proteases capable of completely degrading all internalized polypeptides, Retention of some acid hydrolases in endosomes is apparently related to their association with undefined endosomal membrane receptors, The limited number of proteases and the pH gradient from neutral to acidic (pH 7 to 5) within endosomes make possible a selective and controlled processing environment in comparison to lysosomes, The full set of endo- and exopeptidases that break down proteins to amino acids are active later in the pathway in lysosomes.