Endosomal proteolysis of internalized proteins

Abstract

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.Key words: Endosomes; Endocytosis; Major histocompatibility complex class II; Antigen processing; Endopeptidase; Cathepsin (insulin, glucagon, epidermal growth factor (EGF), invariant chain (Ii), antibodies and vitellogenin) and activation (lysosomal hydrolases, parathyroid hormone (PTH), protein antigens and toxins) of internalized proteins. The intraendosomal cleavage of proteins following endocytosis has been studied in a large number of cells, especially hepatocytes, macrophages, B-lymphocytes, fibroblasts and oocytes. These studies have raised interesting questions regarding the extent of endosomal proteolysis in different cell types, the nature and specificity of endosomal proteases, the points in the endocytic pathway where acid hydrolases are delivered and the mechanisms by which proteases are permanently retained within endosomes. Furthermore, recent studies have demonstrated that the cysteine protease cathepsins B and H, and the aspartic protease cathepsin D play a particularly important role in endosomal proteolysis. The present review focuses on the endosomal pathways involved in the processing of polypeptide hormones and internalized antigenic proteins. Proteolytic modifications of internalized proteins in endosomes

Metal ions affect insulin-degrading enzyme activity

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The Nipah Virus Fusion Protein Is Cleaved within the Endosomal Compartment

“…as a major sorting station of the endocytic pathway and receive endocytosed materials from the cell surface for recycling or transport to late endosomes and lysosomes, it is now well accepted that endosomes also represent a biologically important processing compartment within cells (29,30). Endosomal cathepsins, metalloproteases, and secretases mediate cleavage or limited proteolysis of a variety of cellular proteins, leading either to degradation or activation of the respective proteins (31)(32)(33)(34)(35)(36)(37)(38).…”

Pathway for Degradation of Peptides Generated by Proteasomes

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