THE GLYCEROPHOSPHOINOSITOLS IN THE MODULATION OF THE RHO GTPASES, ACTIN DYNAMICS, AND ACTIN-RELATED DISEASES

In recent years it has become clear that several genetic disorders are targeted at gene products which are important modulators of the cellular cytoskeleton, the complex network of specific proteins that determines cell shape and motility. The cytoskeleton is also highly dynamic, and is modulated by the assembly/disassembly of specific proteins (machinery). Actin is one of the main component of this cellular cytoskeleton and is modulated by the actin dynamics machinery. In particular, we are interested in this actin dynamics machinery. Several of the proteins modulating this machinery are seen to be mutated, and thus to misfunction, in genetic disorders such as Wiskott-Aldrich Syndrome (WAS), non-specific mental retardation (MRX), and Alzheimer’s disease. The aim of our project is to study the components of the cellular cytoskeleton of the actin dynamics machinery using some natural compounds (the glycerophosphoinositols) that have been characterized in our laboratory and have the peculiarity of directly controlling several steps of the actin cytoskeleton organization. We believe that by using these compounds as molecular tools we will be able to better understand the functioning of the actin dynamics machinery, and thus the related cellular functions (cell shape and motility). Moreover, we plan to assess the pharmacological potential of these glycerophosphoinositols, with the aim of using them in the development of specific drugs for actin-related diseases.