PATHOGENESIS OF FACIOGENITAL DYSPLASIA: THE ROLE OF FGD1 IN REGULATION OF MEMBRANE TRANSPORT

In recent years, it has become clear that several genetic disorders are targeted at gene products that are important regulators of protein transport in cells, the process whereby newly synthesized proteins travel to their functional sites, and which involves numerous membrane organelles. These membrane organelles are thus highly dynamic, and are modulated by the assembly/disassembly of specific proteins complexes (machineries). One of these machineries includes Cdc42, a protein regulating transport and targeting of numerous proteins, and its activator protein FGD1. We are particularly interested in this machinery because mutations in FGD1 lead to the genetic disorder known as faciogenital dysplasia (FGDY, Aarskog syndrome), which is characterized by multiple bone, genital and ophthalmic abnormalities, and by mental retardation. However, the questions of how these FGD1 mutations affect protein transport and how this contributes to the pathogenesis of FGDY remain to be answered. The aim of our project is to study the role of FGD1 in the regulation of protein transport and to understand the importance of this process for FGDY development. Therefore, by using the expertise and advanced technical tools available in our Department, we intend not only to provide answers for the above questions, but also to describe model systems of FGDY for their use in drug or gene therapy testing.