Keratinocytes

BrixResearch_KC_migration_scheme
Research Projects Brix – Keratinocytes

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

References:

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

  • Arampatzidou, M., M. Rehders, S. Dauth, D.M.T. Yu, S. Tedelind, and K. Brix (2011). Imaging of protease functions – current guide to spotting cysteine cathepsins in classical and novel scenes of action in mammalian epithelial cells and tissues. It. J. Anat. Embryol. 116, 1-19.
  • Rehders, M., B.B. Grosshäuser, A. Smarandache, A. Sadhukhan, U. Mirastschijski, J. Kempf, M. Dünne, K. Slenzka, and K. Brix (2011). Effects of lunar and mars dust simulants on HaCaT keratinocytes and CHO-K1 fibroblasts. Adv. Space Res. 47, 1200-1213. doi:10.1016/j.asr.2010.11.033
  • Donfack, P., M. Rehders, K. Brix, P. Boukamp, and A. Materny (2010). Micro Raman spectroscopy for monitoring alterations between human skin keratinocytes HaCaT and their tumorigenic derivatives A5RT3 – toward a Raman characterization of a skin carcinoma model. J. Raman Spectrosc. 41, 16-26. doi:10.1002/jrs.2400
  • Brix, K., A. Dunkhorst, K. Mayer, and S. Jordans (2008). Cysteine cathepsins: Cellular roadmap to different functions. Biochimie 90, 194-207. doi:10.1016/j.biochi.2007.07.024
  • 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
  • Büth, H., P.L. Buttigieg, R. Ostafe, M. Rehders, S.R. Dannenmann, N. Schaschke, H.-J. Stark, P. Boukamp, and K. Brix (2007). Cathepsin B is essential for regeneration of scratch-wounded normal human epidermal keratinocytes. Eur. J. Cell Biol. 86, 747-76. doi:10.1016/j.ejcb.2007.03.009
  • 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.