In particular we plan to characterize Ca2+- and Na+-activated K+ channels (e.g. slick and slack channels)...
Department of Molecular Pharmacology
Innsbruck Medical University
Univ.-Prof. Dr. med.
Ion channels are important constituents of many signalosomic complexes. They are crucial with respect to intrinsic electrical properties of neurons, how these cells respond to external stimuli, how they integrate the encoded information and as a result, generate appropriate responses.
Sequencing the human genome yielded the precise number of such voltage-gated ion channel subunits which are generally accepted to be co-assembled in complexes. These microdomains may consist of additional membrane proteins, a number of scaffolding proteins, and different intracellular components with catalytic functions.
Since we have generated and characterized a large panel of selective tools (e.g. antibodies, labeled toxin analogues) over the past decade, this proposal aims towards the characterization of a limited number of micro-domains containing ion channels. In particular we plan to characterize Ca2+- and Na+-activated K+ channels (e.g. slick and slack channels) of which very recently gene-product-deficient animals became available. After detergent-solubilization, native ion channel complexes are immunopreciptated together with partnering proteins and analysed by mass sprectromety. Follow-up experiments are going to aim towards a functional characterization of newly discovered partners.
Berkefeld, H., Sailer, C.A., Bidl, W., Thumfart, J.O., Rhode, V., Eble, S., Klugbauer, N., Reisinger, E., Bischofberger, J., Oliver, D., Knaus, H.G., Schulte, U. & Fakler B.: BKCa-Cav channel complexes mediate rapid and localized Ca2+-activated K+ signalling; Science 314, 615-620 (2006)
Schulte, U., Thumfart, J.-O., Klöcker, N., Sailer, C.A., Bildl, W., Biniossek, M., Dehn, D., Deller, T., Eble, S., Abbass, K., Wangler, T., Knaus, H.G. & Fakler, B.: The epilepsy-linked Lgi1 protein assembles into presynaptic Kv1 channels and inhibits inactivation by Kvß1; Neuron, 49, 697-706 (2006)
Müller CS, Haupt A, Bildl W, Schindler J, Knaus, H.G., Meissner M, Rammner B, Striessnig J, Flockerzi V, Fakler B. & Schulte U.: Quantitative proteomics of the Cav2 channel nano-environments in the mammalian brain. Proc Natl Acad Sci U S A. 24;107(34):14950-7 (2010).