Abstract
Kallikrein-related proteases (KLKs) play a critical role in epidermis physiology and have been implicated in skin pathologies such as Netherton syndrome. The contribution of individual KLKs to skin proteolysis is poorly understood. Monitoring of their activities in skin proteome is hampered by overlapping substrate specificities, and there is a need for novel assays. Here, we present a platform of selective and sensitive fluorogenic substrates and inhibitors for profiling KLK5, KLK7 and KLK14. These chemical tools were evaluated using recombinant KLKs and tissue from a unique set of mice deficient in eight combinations of KLKs and their natural regulator LEKTI.
Acknowledgements
The study was supported by projects InterBioMed LO1302 to M.H., J.S. and M.M., LM2015040 ‘Czech Centre for Phenogenomics’ and LQ1604 ‘National Sustainability Program II (NPUII)’ to R.S. funded by the Ministry of Education, Youth and Sports and CZ.1.05/2.1.00/19.0395 grant for ‘Higher quality and capacity for transgenic models’ to R.S. funded by the Ministry of Education, Youth and Sports and the European Regional Development Fund., by Benevolent fund for support of science – Neuron to P.K. and also by Academy of Sciences of the Czech Republic (Funder Id: 10.13039/501100004240) (RVO 61388963 and RVO 68378050).
References
Beaufort, N., Plaza, K., Utzschneider, D., Schwarz, A., Burkhart, J.M., Creutzburg, S., Debela, M., Schmitt, M., Ries, C., and Magdolen, V. (2010). Interdependence of kallikrein-related peptidases in proteolytic networks. Biol. Chem. 391, 581–587.10.1515/bc.2010.055Search in Google Scholar
Borgono, C.A., Michael, I.P., Komatsu, N., Jayakumar, A., Kapadia, R., Clayman, G.L., Sotiropoulou, G., and Diamandis, E.P. (2007). A potential role for multiple tissue kallikrein serine proteases in epidermal desquamation. J. Biol. Chem. 282, 3640–3652.10.1074/jbc.M607567200Search in Google Scholar PubMed
Caubet, C., Jonca, N., Brattsand, M., Guerrin, M., Bernard, D., Schmidt, R., Egelrud, T., Simon, M., and Serre, G. (2004). Degradation of corneodesmosome proteins by two serine proteases of the kallikrein family, SCTE/KLK5/hK5 and SCCE/KLK7/hK7. J. Invest. Dermatol. 122, 1235–1244.10.1111/j.0022-202X.2004.22512.xSearch in Google Scholar PubMed
Chao, J., Bledsoe, G., Yin, H., and Chao, L. (2006). The tissue kallikrein-kinin system protects against cardiovascular and renal diseases and ischemic stroke independently of blood pressure reduction. Biol. Chem. 387, 665–675.10.1515/BC.2006.085Search in Google Scholar PubMed
de Veer, S.J., Swedberg, J.E., Parker, E.A., and Harris, J.M. (2012). Non-combinatorial library screening reveals subsite cooperativity and identifies new high-efficiency substrates for kallikrein-related peptidase 14. Biol. Chem. 393, 331–341.10.1515/bc-2011-250Search in Google Scholar PubMed
de Veer, S.J., Furio, L., Harris, J.M., and Hovnanian, A. (2014). Proteases: common culprits in human skin disorders. Trends Mol. Med. 20, 166–178.10.1016/j.molmed.2013.11.005Search in Google Scholar PubMed
de Veer, S.J., Furio, L., Swedberg, J.E., Munro, C.A., Brattsand, M., Clements, J.A., Hovnanian, A., and Harris, J.M. (2017). Selective substrates and inhibitors for kallikrein-related peptidase 7 (KLK7) shed light on KLK proteolytic activity in the stratum corneum. J. Invest. Dermatol. 137, 430–439.10.1016/j.jid.2016.09.017Search in Google Scholar PubMed
Descargues, P., Deraison, C., Bonnart, C., Kreft, M., Kishibe, M., Ishida-Yamamoto, A., Elias, P., Barrandon, Y., Zambruno, G., Sonnenberg, A., et al. (2005). Spink5-deficient mice mimic Netherton syndrome through degradation of desmoglein 1 by epidermal protease hyperactivity. Nat. Genet. 37, 56–65.10.1038/ng1493Search in Google Scholar PubMed
Fajtova, P., Stefanic, S., Hradilek, M., Dvorak, J., Vondrasek, J., Jilkova, A., Ulrychova, L., McKerrow, J.H., Caffrey, C.R., Mares, M., et al. (2015). Prolyl oligopeptidase from the blood fluke Schistosoma mansoni: from functional analysis to anti-schistosomal inhibitors. PLoS Negl. Trop. Dis. 9, e0003827.10.1371/journal.pntd.0003827Search in Google Scholar PubMed PubMed Central
Kasparek, P., Krausova, M., Haneckova, R., Kriz, V., Zbodakova, O., Korinek, V., and Sedlacek, R. (2014). Efficient gene targeting of the Rosa26 locus in mouse zygotes using TALE nucleases. FEBS Lett. 588, 3982–3988.10.1016/j.febslet.2014.09.014Search in Google Scholar PubMed
Kasparek, P., Ileninova, Z., Zbodakova, O., Kanchev, I., Benada, O., Chalupsky, K., Brattsand, M., Beck, I.M., and Sedlacek, R. (2017). KLK5 and KLK7 ablation fully rescues lethality of Netherton syndrome-like phenotype. PLoS Genet. 13, e1006566.10.1371/journal.pgen.1006566Search in Google Scholar PubMed PubMed Central
Lundwall, A. and Brattsand, M. (2008). Kallikrein-related peptidases. Cell Mol. Life Sci. 65, 2019–2038.10.1007/s00018-008-8024-3Search in Google Scholar PubMed
Sales, K.U., Masedunskas, A., Bey, A.L., Rasmussen, A.L., Weigert, R., List, K., Szabo, R., Overbeek, P.A., and Bugge, T.H. (2010). Matriptase initiates activation of epidermal pro-kallikrein and disease onset in a mouse model of Netherton syndrome. Nat. Genet. 42, 676–683.10.1038/ng.629Search in Google Scholar PubMed PubMed Central
Stopkova, R., Klempt, P., Kuntova, B., and Stopka, P. (2017). On the tear proteome of the house mouse (Mus musculus musculus) in relation to chemical signalling. Peer J. 5, e3541.10.7717/peerj.3541Search in Google Scholar PubMed PubMed Central
Tamura, H., Ishikawa, Y., Hino, N., Maeda, M., Yoshida, S., Kaku, S., and Shiosaka, S. (2006). Neuropsin is essential for early processes of memory acquisition and Schaffer collateral long-term potentiation in adult mouse hippocampus in vivo. J. Physiol. 570, 541–551.10.1113/jphysiol.2005.098715Search in Google Scholar PubMed PubMed Central
Yoon, H., Laxmikanthan, G., Lee, J., Blaber, S.I., Rodriguez, A., Kogot, J.M., Scarisbrick, I.A., and Blaber, M. (2007). Activation profiles and regulatory cascades of the human kallikrein-related peptidases. J. Biol. Chem. 282, 31852–31864.10.1074/jbc.M705190200Search in Google Scholar PubMed
Supplementary Material:
The online version of this article offers supplementary material (https://doi.org/10.1515/hsz-2018-0116).
©2018 Walter de Gruyter GmbH, Berlin/Boston
