Research Topic
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.
Selected Publications
Alavizargar, A., Gass, M., Krahn, MP. and Heuer, A. (2024) Elucidating the Membrane Binding Process of a Disordered Protein: Dynamic Interplay of Anionic Lipids and the Polybasic Region. ACS Physical Chemistry Au. Jan 18;4(2):167-179. doi: 10.1021/acsphyschemau.3c00051.
Fiedler, F., Moennig, T., Hinrichs, JH., Weber, A., Wgner, T., Hemmer, T., Schröter, R., Weide, T., Epting, D., Bergmann, C., Nedvetsky, P., and Krahn, MP. (2023) PATJ inhibits histone deacetylase 7 to control tight junction formation and cell polarity. Cell Mol Life Sciences, Oct 25;80(11):333. doi:10.1007/s00018-023-04994-3.
Borkowsky, S., Gass, M., Alavizargar, A., Hanewinkel, J., Hallstein, I., Nedvetsky, P., Heuer, A., and Krahn, MP. (2023) Phosphorylation of LKB1 by PDK1 Inhibits Cell Proliferation and Organ Growth by Decreased Activation of AMPK. Cells. 12(5):812. doi: 10.3390/cells12050812.
Gass, M., Borkowsky, S., Schröter, R., Nedvetsky, P., Luschnig, S., Rohlmann, A., Missler, M., and Krahn, MP. (2022) Phosphoinositides are essential regulators of slit diaphragm integrity and nephrocyte function. Cell Mol Life Sciences, 79(5):248. doi: 10.1007/s00018-022-04273-7.
Lüttgenau, S.M., Emming, C., Wagner, T., Harms, J., Guske, J., Weber, K., Neugebauer, U., Schröter, R., Panichkina, O., Pethö, Z., Weber, F., Schwab, A., Wege, A.K., Nedvetsky, P., and Krahn, MP. (2021). Pals1 prevents Rac1-dependent colorectal cancer cell metastasis by inhibiting Arf6. Molecular Cancer. 20(1):74. doi.org/10.1186/s12943-021-01354-2