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SFB-F44 - Cell signaling in chronic CNS disorders

Project 06:
L-type Ca2+ channel  signaling complexes and epigenetic mechanisms induced by Ca2+ channel to nucleus signaling

Bernhard E. Flucher and Gerald Obermair

In cultured CNS neurons we study the specific functions of distinct L-type Ca2+ channel splice variants recently characterized within our consortium to better understand their potential role in the etiology of Parkinson's disease. Using established mRNA expression profiling we will characterize the exact isoform composition of such channel complexes in relevant neurons. We will also generate tagged channels to analyze the differential targeting properties of these splice variants in hippocampal neurons and the roles of their interaction with known scaffold proteins for dendritic stability and remodeling. Because our recent findings indicate that some Ca2+ channel beta-subunits are targeted into the nucleus of quiescent neurons, we will characterize the composition of nuclear beta-protein complexes and investigate their role for epigenetic signaling and transcriptional regulation.