Role of Ena/VASP proteins in homeostasis and disease.

The actin cytoskeleton is required for many important processes during embryonic development. In later stages of life, important homeostatic processes depend on the actin cytoskeleton, such as immune response, haemostasis and blood vessel preservation. Therefore, the function of the actin cytoskeleton must be tightly regulated, and aberrant regulation may cause disease. A growing number of proteins have been described to bind and regulate the actin cytoskeleton. Amongst them, Ena/VASP proteins function as anti-capping proteins, thereby directly modulating the actin ultrastructure. Ena/VASP function is regulated by their recruitment into protein complexes downstream of plasma membrane receptors and by phosphorylation. As regulators of the actin ultrastructure, Ena/VASP proteins are involved in crucial cellular functions, such as shape change, adhesion, migration and cell-cell interaction and hence are important targets for therapeutic intervention. In this chapter, we will first describe the structure, function and regulation of Ena/VASP proteins. Then, we will review the involvement of Ena/VASP proteins in the development of human diseases. Growing evidence links Ena/VASP proteins to important human diseases, such as thrombosis, cancer, arteriosclerosis, cardiomyopathy and nephritis. Finally, present and future perspectives for the development of therapeutic molecules interfering with Ena/VASP-mediated protein-protein interactions are presented.