Section Days abstract book 2010.indd - RUB Research School ...

LS_10
Investigations on the role of selected ionotropic glutamate
receptors during neural development in vitro
Svenja Pachernegg, Sebastian Eilebrecht, Elke Muth-Köhne, Gloria Fuhrmann,
Michael Hollmann
Department of Biochemistry I; Ruhr-Universität Bochum, 44780 Bochum, Germany
International Graduate School of Neuroscience, 44780 Bochum, Germany
e-mail: Svenja.Pachernegg@rub.de
Ionotropic glutamate receptors (iGluRs) mediate the majority of excitatory neurotransmission
in the vertebrate CNS. To examine the involvement of iGluRs during both embryonic and
neonatal/adult neurogenesis two major approaches were followed: First, the function of the
NMDAR subunit NR3A in neural stem cells (NSCs) was investigated via the use of RNA
interference. After the downregulation of NR3A, DNA microarray analysis revealed that the
expression of more than 500 genes is significantly affected. The protein products of two of the
genes affected have been previously shown to interact with NMDARs.
In a second approach, the editing state of the AMPAR subunit GluR2 in neural cell types was
investigated. GluR2 can undergo RNA editing at the Q/R site which renders AMPARs
calcium-impermeable. We have examined the expression of GluR2 and of its editing enzyme
ADAR2. Possibly, a pool of ADAR2 is established in ESCs before the expression of GluR2
commences, so that all GluR2 subunits can be edited as soon as they are expressed.
Unexpectedly, 100% of GluR2 in NEPs and 97% of GluR2 in NSCs were found to be edited,
contradicting literature data and pointing to the crucial role of Q/R editing, as all GluR2
subunits in NEPs appear to be edited as soon as they are expressed.