BIOPHYSICS CONGRESS 2015

Identification and Characterization of Proteins and Lipids Associated to Regulators of Cell Excitability

Identification and Characterization of Proteins and Lipids Associated to Regulators of Cell Excitability

Potassium selective ionic channels play a key role in processes such as immune response, cell differentiation, excitability and cell death, among others. Mutations in some subunits of potassium channels are the cause of many hereditary diseases known as channelopathies. To date, around 10 potassium channelopathies have been identified and four of these are due to mutations in genes of the KCNQ family, the gene products of which are Kv7.1-Kv7.5. Our research is focused on the molecular study of these proteins that regulate cell excitability. In humans, mutations of these proteins cause arrhythmia, epilepsy and deafness, depending on the isoform affected and their distribution within the tissue. Our objective is to identify the network of proteins associated with these channels, by analyzing the physiological consequences of these interactions through mutagenesis function studies, and the use of electrophysiological, imaging, biochemical and high-resolution biophysical techniques.

In adition, we aim to determine the role played by lipids in the regulation of these channels. Currently, we are establishing the channel regions involved in biogenesis, assembly, membrane insertion and subcellular localization, as well as in the regulation by lipid second messengers. We hope to identify the proteins and lipids that interact specifically with each of these domains, and these may become targets for the therapeutic drug development. In the longer term, our objective is to determine the three-dimensional structure of these macro-complexes. As an intermediate stage, en route to future crystallization, we are investigating new strategies for high-yield production of large quantities of water-soluble, properly folded macro-complexes.

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