During regeneration from wounding, secreted cathepsin B mediates keratinocyte migration for rapid wound closure by proteolysis and remodeling of the extracellular matrix. Specific receptors at the plasma membrane ensure restriction of the proteolytic activity of cathepsin B to the basal pole of the migratory cells. In contrast, trafficking of cathepsins L and V follow different routes in keratinocytes. Cathepsin L remains largely unaffected by the wounding of a human keratinocyte cell line. However, a truncated version of cathepsin V is translocated to the nuclei of regenerating cells before keratinocytes start to proliferate. Future experiments aim to verify a causal relation between these two events and shall elucidate the molecular mechanisms that are initiated by the appearance of cathepsin V within the nuclei of keratinocytes.
Supported by DFG BR1308 / 6-1, 6-2
BOOK CHAPTER: Brix, K., C.J. Scott, M.M.S. Heck (2013) Compartmentalization of Proteolysis. In: Proteases: Structure and Function, edited by Klaudia Brix and Walter Stöcker, Springer-Verlag, Wien. http://www.springer.com/gp/book/9783709108840#otherversion=9783709108857
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- Ong, P.C., S. McGowan, M.C. Pearce, J.A. Irving, W.-T.Kan, S.A. Grigoryev, B. Turk, G.A. Silverman, K. Brix, S.P. Bottomley, and J.C. Whisstock, R. Pike (2007). DNA accelerates the inhibition of human cathepsin V by serpins. J. Biol. Chem. 282, 36980-36986. doi:10.1074/jbc.M706991200
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- Büth, H., B. Wolters, B. Hartwig, R. Meier-Bornheim, H. Veith, M. Hansen, C.P. Sommerhoff, N. Schaschke, W. Machleidt, N.E. Fusenig, P. Boukamp, and K. Brix (2004). HaCaT keratinocytes secrete lysosomal cysteine proteinases during migration. Eur. J. Cell Biol. 83, 781-795.