Potassium channels contribute to the control of cell volume, membrane potential, neuronal excitability, and the secretion of salts, hormones and neurotransmitters. Their activities are regulated by a number of factors including the electrical potential across the cell membrane, cytosolic calcium and ATP and by the action of various kinases/phosphatases and other accessory proteins. It has been recently shown that two members of an ecto-peptidase family, DPP6 and DPP10, whose function was previously unknown, may interact with some voltage-gated channels of the Kv4 family and affect their properties, through a mechanism still unknown.
This project is focussed on the elucidation of the physiological role of DPP6 and DPP10 through the identification of their bin ding partners (included putative substrate proteins) and characterization of their structure-function relationships. These data will be useful for the development of inhibitory molecules for pharmacological or therapeutic use. In order to achieve this result we propose an innovative and interdisciplinary approach, based on novel HTS selection of interacting partners.
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