Specific functions of lysosomal proteases in endocytic and autophagic pathways

Abstract

Endolysosomal vesicles form a highly dynamic multifunctional cellular compartment that contains multiple highly potent proteolytic enzymes. Originally these proteases have been assigned to cooperate solely in executing the unselective 'bulk proteolysis' within the acidic milieu of the lysosome. Although to some degree this notion still holds true, evidence is accumulating for specific and regulatory functions of individual 'acidic' proteases in many cellular processes linked to the endosomal/lysosomal compartment. Here we summarize and discuss the functions of individual endolysosomal proteases in such diverse processes as the termination of growth factor signaling, lipoprotein particle degradation, infection, antigen presentation, and autophagy. This article is part of a Special Issue entitled: Proteolysis 50 years after the discovery of lysosome.

A Brucella spp. Protease Inhibitor Limits Antigen Lysosomal Proteolysis, Increases Cross-Presentation, and Enhances CD8+ T Cell Responses

“…by guest on May 12, 2018 http://www.jimmunol.org/ mouse TLR2, 3,4,7,8,9, and 13 or mouse Nod-like receptors (NOD1 and NOD2) (data not shown). Importantly, note that at present there are adjuvants used in human vaccine formulations, such as MF59, known to have important inflammatory properties and that are safe, but to which their innate receptor has not been found until present.…”

“…Lysosomal proteases are crucial in many cellular processes such as Ag presentation by APCs (6)(7)(8)(9). Besides, it has been reported that the extraordinary function of DCs as professional APCs could be explained by their particular moderate proteolytic activity (10).…”

PCSK9-mediated degradation of the LDL receptor generates a 17 kDa C-terminal LDL receptor fragment

“…However, the mannose-6-phosphate receptor is not specifi c for late endosomes and cathepsin D is not specifi c for lysosomes. Rather, they are found in various amounts also in other organelles of the endosomal/lysosomal tract, including early endosomes ( 38,(44)(45)(46). Endosomal proteases may in fact themselves undergo proteolytic maturation down the endosomal/ lysosomal tract as has been found for cathepsin D ( 47 ).…”

Pathways of Antigen Processing

“…Antigen processing in these vesicles is influenced by their pH, which regulates the activity of resident proteases and other relevant enzymes, such as gamma interferon inducible lysosomal thiol reductase (GILT, Figure 4) (140-142). Differences in the ability of distinct APCs to regulate endocytic processing have also been documented.…”