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Cathepsins: Getting in Shape for Lysosomal Proteolysis

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Proteases: Structure and Function

Abstract

Besides their pivotal functions in general cellular protein turnover, cathepsins play important roles in a diverse range of other physiological processes which include tissue remodelling during embryogenesis and development, programmed cell death, autophagy, prohormone and neuropeptide processing, antigen presentation, wound healing and bone resorption. Furthermore, substantial experimental evidence has been accumulated that cathepsins are of pathological relevance in disease states such as cancer, arthritis, osteopetrosis, pancreatitis, cholestatic liver disease, and epilepsy (Mohamed and Sloane 2006; Vasiljeva et al. 2007; Turk and Turk 2009; Reiser et al. 2010). To prevent tissue damage due to unwanted proteolysis, the activities of cathepsins have to be strictly controlled in situ. The main regulatory pathways rely on restricting the subcellular localization of these proteases to lysosomes, the presence of specific cathepsin inhibitors in other cellular compartments, and their initial synthesis as latent proenzymes (Cygler and Mort 1997; Mort and Buttle 1997; Turk et al. 2001b). Interference with any of these control mechanisms can lead to pathological consequences. It is therefore crucial to understand the molecular basis of cathepsin biosynthesis and intracellular transport as well as the mechanisms leading to activation of their precursors in a cellular context.

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Acknowledgements

This article is based on work funded by the United States National Science Foundation (MCB-8908842, 9204834, 9604139 and 0235680; A.H.E.), Fondazione Compagnia S. Paolo (Neuroscienze, 2008.2395; C.I.) and Polo di Innovazione Tecnologica (POR-FESR, BANP 2010; C.I.). Molecular structures were prepared using the program PyMOL (http://sourceforge.net/projects/pymol/).

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  1. Department of Biochemistry and Biophysics, University of North Carolina, Chapel Hill, NC, USA

    Ann H. Erickson

  2. Department of Medical Sciences, Amedeo Avogadro University, Novara, Italy

    Ciro Isidoro

  3. Department of Applied Genetics and Cell Biology, University of Natural Resources and Life Sciences, Muthgasse 18, 1190, Vienna, Austria

    Lukas Mach

  4. Genetics Unit, Shriners Hospital for Children, Montreal, Canada

    John S. Mort

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Correspondence to Lukas Mach .

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  1. SCHOOL OF ENGINEERING AND SCIENCE, JACOBS UNIVERSITY BREMEN, Bremen, Germany

    Klaudia Brix

  2. Institute of Zoology, Johannes Gutenberg University Mainz, Mainz, Germany

    Walter Stöcker

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Erickson, A.H., Isidoro, C., Mach, L., Mort, J.S. (2013). Cathepsins: Getting in Shape for Lysosomal Proteolysis. In: Brix, K., Stöcker, W. (eds) Proteases: Structure and Function. Springer, Vienna. https://doi.org/10.1007/978-3-7091-0885-7_4

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