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P 16 - Prof. Dr. Bernd Fakler

Analysis of the protein nano-environments of the voltage-gated P/Q-type Ca2+ channels Cav2.1 in the brain



Prof. Dr. Bernd Fakler

Institut für Physiologie II

Hermann-Herder-Str. 7

79104 Freiburg

Phone: +49 761 203-5175

Fax: +49 761 203-5191



Project Summary


Voltage-gated Ca2+ (Cav) channels are key elements linking excitability to a large variety of cellular processes via local Ca2+ signalling that occurs in defined spatial domains around the Cav channels, termed nano-environments. As the molecular basis behind nano-environments we have identified extended protein networks resulting from co-assembly of Cav channels with distinct partner proteins and subsequent cross-interactions between individual modules (network strings). Using proteomic techniques and functional recordings we have characterized some of these strings including those of Cav2 channels with GABAB receptors, Ca2+-activated ion channels and Ca2+-controlled enzymatic activities.
The central goal of our future studies is understanding of the protein networks and functional modules assembled with Cav2.1 channels with focus on the following main issues: Significance of the network arrangement and of individual modules for the Cav-driven local Ca2+-signalling in
neurons, structure-function analyses of individual modules in vitro and in vivo, mechanisms and steps underlying formation of Cav2-associated protein networks, as well as architecture and connectivities of the protein networks. For the proposed analyses we will interactively apply an array of techniques including high-resolution proteomics, biochemistry, electron and fluorescence-based microscopy, functional recordings of Ca2+ signalling in Cav  nanoenvironments before and after manipulation by virus-directed expression of shRNAs and/or protein.

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