Structure and Function of Villin

Villin is an epithelial cell‐specific protein that belongs to a family of actin‐binding proteins that display structural and functional homology and include among other proteins, gelsolin, severin, fragmin, adseverin/scinderin, supervillin, and protovillin. Villin is unique among these proteins in that it can sever, cap, nucleate, and crosslink actin filaments. The actin modifying functions of villin are regulated by calcium, phosphoinositides, and tyrosine phosphorylation of the villin protein. Villin also self‐associates and this property of villin is likewise determined by its ligand‐binding properties. Overexpression of villin regulates actin redistribution, cell morphology, cell migration, and cell death. Studies done with the villin knockout mice substantiate the significance of villin in actin reorganization and maintenance of epithelial cell plasticity. In this chapter I discuss how the ligand‐binding properties of villin are mechanistically important to its functions in cell migration and cell death.