The establishment of cell-cell-contacts and the determination of an apical-basal polarity is a crucial prerequisite for the integrity and functionality of epithelial tissues. In our group, we aim to investigate the cellular and molecular mechanisms controlling the establishment and maintenance of apical-basal cell polarity in Drosophila and mammalian cells with a particular emphasis on the link between cell polarity and cell proliferation control / tumorigenesis.
In more detail, we investigate how the localization and activation of conserved polarity-regulating kinases (e.g. aPKC, Par-1 and LKB1) and their regulatory adaptor proteins (e.g. PAR-3, Pals1, PATJ) is accomplished by interactions of the proteins with (phospho)lipids of the plasma membrane and how the activity of these kinases is modulated by their adaptor proteins and (phospho)lipids at the (apical) cell-cell contacts. Misregulation of these polarity complexes have been shown to be implicated in severe diseases such as cancer or polycystic kidney disease and the understanding of the molecular pathomechanisms of these diseases might pave the way for the development of new therapies.
- Bayraktar, S., Nehrig, J., Menis, E., Karli, K., Janning,A., Struk, T., Halbritter, J., Michgehl, U., Krahn, M.P., Schuberth, C.E., Pavenstädt, H.P. and Wedlich-Söldner, R. (2020). A deregulated stress response underlies distinct INF2 associated disease profiles. J Am Soc Nephrol. doi:10.1681/ASN.2019111174.
- Krahn, M.P. (2020) Phospholipids of the plasma membrane – regulators or consequence of cell polarity? Front Cell Dev Biol. Apr 28;8:277. doi: 10.3389/fcell.2020.00277.
- Kullmann, L. and Krahn, M.P. (2018) Controlling the master: Upstream regulation of the tumour suppressor LKB1. Oncogene, Jun;37(23):3045-3057.
- Kullmann, L. and Krahn, M.P. (2018) Oligomerization and lipid binding of Par3 function redundantly to promote protein stability and epithelial polarization. Cell Mol Life Sciences, 75(17), 3269-3282.
- Dogliotti, G., Kullmann, L, Dhumale, P., Thiele, C., Panichkina, P., Mendl, G., Houben, R., Haferkamp, S., Püschel, A.W., and Krahn, M.P. (2017) Membrane binding of LKB1 and its activation by phosphatidic acid is essential for its function in development and tumour suppression. Nature Commun. 8, 15747 doi: 10.1038/ncomms15747.
- Hochapfel, F., Mendl, G., Schulze, U., Denk, L., Meese, C., Zaytseva, Y., Pavenstädt, H., Weide, T., Rachel, R., Witzgall, R. and Krahn, M.P. (2017) Distinct function of Crumbs regulating slit diaphragms and endocytosis in Drosophila nephrocytes. Cell Mol Life Sciences. doi: 10.1007/s00018-017-2593-y.
- Cidlinsky, N., Weber, F. and Krahn, M.P. (2016) LKB1 does not contribute to salivary gland tumorigenesis. Cell Oncol, 39(4):389-96.
- Koch, L., Sun, R., Feicht, S., Sen, A. and Krahn, M.P.: Domain-specific functions of Stardust in Drosophila embryonic development Royal Society Open Science. 3(11):160776.
- Sen, A. Sun, R. and Krahn, M.P. (2015) Localization and Function of Pals1 Associated Tight Junction Protein in Drosophila is Regulated by Two Distinct Apical Complexes. J Biol Chem.,290(21):13224-33.
- Sen, A., Nagy-Zsvér-Vadas, Z. and Krahn, M.P. (2012) Drosophila PATJ supports adherens junction stability by modulating Myosin Light Chain activity. J Cell Biol, 199(4):685-98.