Stephanie Wegener
Address:
AG Schmitz
NWFZ - Campus Mitte
Charité Universitätsmedizin Berlin
Charitéplatz 1
10117 Berlin
Germany
Tel +49 (30) 450-639 063
Fax +49 (30) 450-539 943
mailto: stephanie.wegener@charite.de
PhD-Project
"The role of postsynaptic scaffolding proteins in synaptic transmission"
Synopsis
We are interested in the postsynaptic density (PSD) protein Shank3 and investigate its physiological function in hippocampal neurons. The Shank protein family locates to the deep structures of the PSD, a multiprotein complex that reaches from the dendritic cytoskeleton up to the postsynaptic membrane, possibly connecting the various classes of postsynaptic receptors to all kinds of effector proteins. Shanks contain multiple domains for protein interaction, including: an N-terminal ankyrin repeat domain, an SH3 domain, a PDZ domain that mediates binding to GKAP, a long proline-rich sequence containing binding sites for Homer and cortactin, and a C-terminal SAM domain responsible for multimerisation. Through these domains, Shank interacts with many signaling and scaffolding molecules, suggesting Shank as a major scaffolding protein in the PSD. Furthermore, Shank3 gained a lot of attention for being implicated in autism and for promoting spinogenesis. On a physiological level, however, not much is known about Shank3. Combining molecular techniques (shRNA-mediated protein knock-down in primary neuronal cultures, in utero-electroporation of mice) with electrophysiology (patch-clamp recordings) and possibly also imaging techniques, we hope to shed light on the physiological function of Shank3 in central synapses.
Supervisor
Prof. Dr. med. Dietmar Schmitz
