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.
Kullmann, L. and Krahn, M.P. (2018) Controlling the master: Upstream regulation of the tumour suppressor LKB1.Oncogene, [Epub ahead of print], Mar 15, doi: 10.1038/s41388-018-0145-z.
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, [Epub ahead of print] Mar 10. doi: 10.1007/s00018-018-2792-1.
Hochapfel, F., Denk, L., Maaßen, C., Zaytseva, Y., Rachel, R., Witzgall, R. and Krahn, MP. (2018) Electron microscopy of Drosophila garland cell nephrocytes: optimal preparation, immunostaining and STEM tomography. J Cell Biochem. doi: 10.1002/jcb.26702. [Epub ahead of print].
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.
Weide, T., Vollenbroker, B., Djuric, I., Edeling, M., Bonse, J., Hochapfel, F., Panichkina, O., Schulze, U., Wennmann, D-O., George, B., Kim, S., Daniel, C., Seggewiss, J., Walsh, C.A., Amann, K., Kritz, W., Krahn, M.P. and Pavenstaedt, H. (2017) Pals1 haploinsufficiency in nephrons results in proteinuria and cyst formation. J Am Soc Nephrol. Feb 2. pii: ASN.2016040474.
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.
Krahn, M.P., Klopfenstein, D., Fischer, N. and Wodarz, A. (2010). Membrane targeting of Bazooka/PAR-3 is mediated by direct binding to phosphoinositide lipids. Curr Biol, 20:636-42.
Krahn, M.P., Bückers, J., Kastrup, L. and Wodarz, A. (2010). Formation of a Bazooka/Stardust complex is essential for plasma membrane polarity in epithelia. J Cell Biol, 190(5):751-60.
Krahn, M.P., Egger-Adam, D. and Wodarz, A. (2009). PP2A antagonizes phospho-rylation of Bazooka by PAR-1 to control apical-basal polarity in dividing embryonic neuroblasts. Dev Cell, 16: 901-908.