Cathepsins: Fundamental Effectors of Endolysosomal Proteolysis

Abstract

Intracellular protein degradation is a universal feature of eukaryotic cells and vital for nutrition, protein turnover, intracellular signaling, development and other major physiological processes like antigen presentation and immunity. One of the major compartments of intracellular proteolysis is the endosome-lysosome system. The latter offers a highly orchestrated, vesicular pathway for protein transport and ultimate degradation in lysosomes. Though lysosomes are the classical organelles of complex, multi-enzymatic degradation, it is increasingly evident that endosomes conduct much more than mere transport functions. Endosomes contain significant levels of proteases like cathepsins and are sites of potent intracellular proteolysis. Further, discrete classes of endosomes harbor specific cathepsins and perform selective and exclusive functions. Hence, extra-lysosomal proteolytic machinery within the endocytic pathway enjoys spatial and temporal control over proteolytic functions. The review outlines the structural association and function(s) of major endolysosomal cathepsins.