The focus in our lab is the regulation of cell-cell adhesion. We use high-resolution live-cell imaging and biochemical techniques to investigate how cell-cell adhesion receptors
(E-cadherin, Claudin, Nectin) are coupled to the actin cytoskeleton. We study how this linkage is organized to establish proper de-novo cell-cell adhesion and how this linkage is affected to regulate remodeling of cell-cell adhesion during processes that underlie HGF-induced metastasis and neo-angiogenesis. In each of these processes, forces generated by contractility in the cytoskeleton play an important role. Thus, ultimately, we wish to understand how the protein complexes that form the link between cell-cell junctions and actin can sense changes in force and orchestrate a cellular response.
About the research
Lyle, K.S., Raaijmakers, J.H., Bruinsma, W., Bos, J.L., de Rooij, J. (2008) cAMP-induced Epac-Rap activation inhibits epithelial cell migration by modulating focal adhesion and leading edge dynamics. Cell Signal. 20: 1104-1116.
Pegtel, D.M., Ellenbroek, S.I., Mertens, A.E., van der Kammen, R.A., de Rooij, J., Collard, J.G. (2007) The Par-Tiam1 complex controls persistent migration by stabilizing microtubule-dependent front-rear polarity. Curr. Biol. 17: 1623-1634.
de Rooij, J., Kerstens, A., Danuser, G., Schwartz, M.A., Waterman-Storer, C.M. (2005) Integrin-dependent acto-myosin contraction regulates epithelial cell scattering. J. Cell Biol. 171: 153-164.
Enserink*, J.M., Christensen*, A.E., de Rooij*, J., van Triest, M.H., Schwede, F., Genieser, H.G., Døskeland, S.O., Blank, J.L., Bos, J.L. (2002) A novel Epac-specific cAMP analogue demonstrates independent regulation of Rap1 and ERK. Nat Cell Biol. 4: 901-906.
de Rooij*, J., Zwartkruis*, F.J., Verheijen, M.H., Cool, R.H., Nijman, S.M., Wittinghofer, A., Bos, J.L. (1998) Epac is a Rap1 guanine-nucleotide-exchange factor directly activated by cyclic AMP. Nature 3;396: 474-477.