| description: |
Main goal of our project is to analyse the role of wolframin in the regulation of the neuroendocrine system and the central nervous system. Specific aim is to evaluate the precise role of wolframin in the posttranslational processing of peptides, what are the targets of wolframin and in which pathways wolframin participates. To answer these questions we need to generate certain model systems - monoclonal antibodies, specific cell lines and transgenic mouse line. By using monoclonal antibodies and cell lines it is possible to analyse the proteins wolframin interacts with. Studies on transgenic mice give us information on the level of organism. We propose that wolframin is related to the activation of enzymes involved in the processing of preprohormones and prepropeptides. One very interesting candidate for our studies is carboxypeptidase E what we suspect to be a main target for wolframin. According to our hypothesis wolframin activates carboxypeptidase E, which in turn can activate the bioactive peptides and hormones. Transgenic animals lacking wolframin gene should reflect the Wolfram syndrome in humans, and it is useful model for us to study the role of wolframin in the regulation of endorine and nervaous system. Additionally we will perfom several behavioural and neurochemical studies. As a result of current project we expect to find out the role of wolframin in the posttranslational processing of peptides and in the regulation of neuroendocrine system. Wolfarmin is newly discovered protein with currently unknown function. |