Universität zu Köln 

Dr. Michael Lammers

Institut für Genetik/CECAD Forschungszentrum
Universität zu Köln
email: mlammers@uni-koeln.de
phone: +49-(0)221 478 84308
website

A key regulator of Rho-proteins is the guanine-nucleotide-dissociation inhibitor RhoGDIα, which binds to prenylated Rho-guanine-nucleotide-binding proteins (RhoGNBPs) and inhibits the nucleotide dissociation of RhoGNBPs. Thereby, RhoGDIα is involved in extracting RhoGNBPs from and delivering them to cellular membranes. Therefore, they play an important role for the activation/inactivation of Rho-signal-transduction pathways. In recent proteomic screens it has been shown that RhoGDIα is lysine-acetylated at four sites. Using the genetic-code expansion concept acetyl-lysine will be recombinantly incorporated into RhoGDIα. We will analyse which effect lysine-acetylation has on RhoGDIα-function. The influence of RhoGDIα-lysine-acetylation on nucleotide-dissociation and on effector binding, on determination of RhoGNBP-specificity and furthermore on the protein structure will be examined. Cellular studies will show if acetylation has an effect on cytoskeletal integrity and RhoGDIα-localisation. Finally, we want to show how RhoGDIα is regulated by lysine-deacetylases (KDACs) and lysine-acetyltransferases (KATs). As a summary, these studies will show how RhoGDIα function is regulated by post-translational lysine-acetylation, why it is acetylated at four sites, which effect acetylation has on cytoskeletal integrity and on RhoGDIα localisation and finally how RhoGDIα-lysine-acetylation itself is regulated.

Running time: 07/2011 – 06/2015

Recent publications:

de Boor, S.*, Knyphausen, P.*, Kuhlmann, N., Wroblowski, S., Brenig, J., Nolte, H., Krüger, M., and Lammers, M. (2015). Small GTP-binding protein Ran is regulated by posttranslational lysine-acetylation. Proc. Natl. Acad. Sci. U. S. A., pii: 201505995. [Epub ahead of print.] *equal first authors PubMed

Lammers, M., Neumann, H., Chin, J.W., and James, L.C. (2010). Acetylation regulates Cyclophilin A catalysis, immunosuppression and HIV isomerization. Nature Chem. Biol. 6, 331-337.

Lammers, M., Meyer, S., Kühlmann, D., and Wittinghofer, A. (2008). Specificity of Interactions between mDia Isoforms and Rho Proteins. J. Biol. Chem. 283, 35236-35246.

Lammers, M., Rose, R., Scrima, A., and Wittinghofer, A. (2005). The regulation of mDia1 by autoinhibition and its release by Rho*GTP. EMBO J. 24, 4176-4187.

Rose, R.*, Weyand, M.*, Lammers, M.*, Ishizaki, T., Ahmadian, M.R., and Wittinghofer, A. (2005). Structural and mechanistic insights into the interaction between Rho and mammalian Dia. Nature 435, 513-518. *equal first authors