Integrins

Integrins are ancient cell adhesion molecules present in all multicellular animals. They not only mediate host cell adhesion to extracellular matrix proteins, but also organize the intracellular actin cytoskeleton and coordinate signal transduction processes at focal adhesion sites. The interplay between different integrin-associated proteins as wells as the regulation of focal adhesion complex assembly and disassembly are key areas of current cell biology research.

Using biochemical and genetic methods, we try to decipher the signals and protein-protein interactions occuring in response to integrin-ligand binding. We are particularly interested in learning how these dynnamic events are translated into orchestrating the cellular cytoskeleton and how they modulate cell adhesion and cell migration. Since a number of pathogenic bacteria highjack integrins to enter cells, we try to elucidate the molecular mechanisms that turn this adhesive proteins into endocytotic receptors.

Recent Publications:

Grimm, T.M., Herbinger, M., Krüger, L., Müller, S., Mayer, T.U., Hauck, C.R. 2022 Lockdown, a selective small-molecule inhibitor of the integrin phosphatase PPM1F, blocks cancer cell invasion. Cell Chem. Biol. 29(6): 930-946.e9. doi:10.1016/j.chembiol.2022.03.011.

Shi, Y., Berking, A., Baade, T., Legate, K.R., Fässler, R., Hauck, C.R. 2021 PIP5KIγ90-generated phosphatidylinositol-4,5-bisphosphate promotes the uptake of Staphylococcus aureus by host cells. Mol. Microbiol. 116(5): 1249-1267. doi:10.1111/mmi.14807.

Grimm, T.M., Dierdorf, N.I., Betz, K., Paone, C., Hauck, C.R. 2020 PPM1F controls integrin activity via a conserved phospho-switch. J. Cell Biol. 219(12): e202001057. doi: 10.1083/jcb.202001057.

Baade, T., Paone, C., Baldrich, A., Hauck, C.R. 2019  Clustering of integrin β cytoplasmic domains triggers nascent adhesion formation and reveals a protozoan origin of the integrin-talin interaction. Sci. Rep. 9(1): 5728. doi: 10.1038/s41598-019-42002-6.

Paone, C., Rodrigues, N., Ittner, E., Santos, C., Buntru, A., Hauck, C.R. 2016 The Tyrosine Kinase Pyk2 Contributes to Complement-Mediated Phagocytosis in Murine Macrophages. Journal of Innate Immunity 8(5): 437-51.

Hauser, M.A., Schaeuble, K., Kindinger, I., Impellizzieri, D., Krueger, W.A., Hauck, C.R., Boyman, O., Legler, D.F. 2016 Inflammation-Induced CCR7 oligomers form scaffolds to integrate distinct signaling pathways for efficient cell migration. Immunity 44:59-72.

Borisova, M., Shi, Y., Buntru, A., Wörner, S., Ziegler, W.H., Hauck, C.R. 2013 Integrin-mediated internalization of Staphylococcus aureus does not require vinculin. BMC Cell Biology 14:2.

Muenzner, P., Bachmann, V., Hentschel, J., Zimmermann, W., Hauck C.R., 2010 Human-specific bacterial pathogens block shedding of epithelial cells by stimulating integrin activation. Science 329: 1197-201.

Hoffmann, C., Berking, A., Agerer, F., Buntru, A., Neske, F., Chhatwal, G.S., Ohlsen, K., HauckC.R. 2010 Caveolin limits membrane microdomain mobility and integrin-mediated uptake of fibronectin-binding pathogens. Journal of Cell Science 123: 4280-91.

Slanina, H., König, A., Hebling, S., Hauck, C.R., Frosch, M., Schubert-Unkmeir, A. 2010
Entry of N. meningitidis into mammalian cells requires Src family protein tyrosine kinases.
Infection and Immunity 78:1905-14.

Traenka, J., Hauck, C.R., Lewandrowski, U., Sickmann, A., Gambaryan, S., Thalheimer, P., Butt E. 2009 Integrin-dependent translocation of LASP-1 to the cytoskeleton of activated platelets correlates with LASP-1 phosphorylation at tyrosine 171 by Src-kinase. Thrombosis and Haemostasis 102: 520-528.

Wu, R., Laser, M., Han, H., Varadarajulu, J., Schuh, K., Hu, K., Ertl, G., Hauck, C.R., Ritter, O. 2006 Fibroblast migration after myocardial infarction is regulated by transient SPARC expression. Journal of Molecular Medicine 84: 241-252.

Stock, C., Gassner, B., Hauck, C.R., Arnold, H., Mally, S., Eble, J.A., Dieterich, P., Schwab, A. 2005 Migration of human melanoma cells depends on extracellular pH and Na+/H+ exchange. Journal of Physiology 567:225-238.

Varadarajulu, J., Laser, M., Hupp, M., Wu, R., Hauck, C.R. 2005 Targeting of alpha_v integrins interferes with FAK activation accompanied by blockage of smooth muscle cell migration and invasion. Biochemical and Biophysical Research Communications 331: 404-412.

Agerer, F., Lux, S., Michel, A., Rohde, M., Ohlsen, K. Hauck, C.R. 2005 Cellular invasion by Staphylococcus aureus reveals a functional link between focal adhesion kinase and cortactin in integrin-mediated internalisation. Journal of Cell Science 118: 2189-2200.