Universitätsstraße 1 40225 Düsseldorf
Our interdisciplinary research group is interested in the identification and functional characterization of integrated biochemical networks and signal transduction pathways involving members of Ras and Rho GTPases, in health and disease.
Mutations in genes encoding a number of regulators and effectors of Rho GTPases are associated with human neurological diseases and X-linked intellectual disabilities and cognitive disorders. In this context, we seek to delineate molecular determinants of axonal plasticity and dendritic spine formation, using straight forward imaging technologies and various molecular approaches, including confocal microscopy, fluorescence spectroscopy, synaptosomal cell fractionation, infection and expression studies.
Currently, we focus on oculocerebrorenal syndrome of Lowe protein (OCRL), oligophrenin (OPHN) and fragile X mental retardation protein (FMRP). Controlling neurite outgrowth, differentiation, and pathfinding, and dendritic spine formation, maintenance, and turn over, these proteins play key roles in various aspects of neuronal development, plasticity, and brain function.
- Frasa, M.A., Koessmeier, K.T., Ahmadian, M.R., Braga, V.M. (2012) Illuminating the functional and structural repertoire of human TBC/RABGAPs. Nat. Rev. Mol. Cell Biol. 13:67-73. PubMed
- Kraft, M., Cirstea, I.C., Voss, A.K., Thomas, T., Goehring, I., Sheikh, B.N., Gordon, L., Scott, H.S., Smyth, G.K., Ahmadian, M.R., Trautmann, U., Zenker, M., Tartaglia, M., Ekici, A., Reis, A., Dörr, H.G. and Rauch, A und Thiel, C.T. (2011) Disruption of the histone acetyltransferase MYST4 leads to a Noonan syndrome-like phenotype and hyperactivated MAPK signaling in humans and mice. J. Clin. Invest. 121, 3479-3491. PubMed
- Cirstea, I.C., Kutsche, K., Dvorsky, R., Gremer, L., Carta, C., Horn, D., Roberts, A.E., Lepri, F., Merbitz-Zahradnik, T., König, R., Kratz, C.P., Pantaleoni, F., Dentici, M.L., Joshi, V.A., Kucherlapati, R.S., Mazzanti, L., Mundlos, S., Patton, M., Cirillo Silengo, M., Rossi, C., Zampino, G., Digilio, C., Stuppia, L., Pennacchio, L.A., Gelb, B.D., Dallapiccola, B., Wittinghofer, A., Ahmadian, M.R.*, Tartaglia, M.* and Zenker, M.* (2010) A restricted spectrum of NRAS mutations causes Noonan syndrome. Nat. Genet. 42, 27-29. PubMed
- Eberth, A., Lundmark, R., Gremer, L., Dvorsky, R., Koessmeier, K.T., McMahon, H.T. and Ahmadian, M.R. (2009) A BAR domain-mediated autoinhibitory mechanism for RhoGAPs of the GRAF family. Biochem. J. 417, 371-377. PubMed
- Hemsath, L., Dvorsky, R., Fiegen, D., Carlier, M.F. and Ahmadian, M.R. (2005) An Electrostatic Steering Mechanism of Cdc42 Recognition by Wiskott-Aldrich Syndrome Proteins. Mol. Cell 20, 313-324. PubMed
- 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. PubMed
- Blochl, A., Blumenstein, L. and Ahmadian, M.R. (2004) Inactivation and activation of Ras by the neurotrophin receptor p75. Eur. J. Neurosci., 20, 2321-2335. PubMed
- Fauchereau, F., Herbrand, U., Chafey, P., Eberth, A., Koulakoff, A., Vinet, M.C., Ahmadian, M.R., Chelly, J.,and Billuart, P. (2003) The RhoGAP activity of OPHN1, a new F-actin binding protein, is negatively controlled by its amino-terminal domain. Mol. Cell. Neurosci. 23, 574-586. PubMed