Murine Epsins Play an Integral Role in Podocyte Function.

Abstract

Epsins, a family of evolutionarily conserved membrane proteins, play an essential role in endocytosis and signaling in podocytes. Podocyte-specific <i>Epn1</i>, <i>Epn2</i>, <i>Epn3</i> triple-knockout mice were generated to examine downstream regulation of serum response factor (SRF) by cell division control protein 42 homolog (Cdc42). Podocyte-specific loss of epsins resulted in increased albuminuria and foot process effacement. Primary podocytes isolated from these knockout mice exhibited abnormalities in cell adhesion and spreading, which may be attributed to reduced activation of cell division control protein Cdc42 and SRF, resulting in diminished <i>β</i>₁ integrin expression. In addition, podocyte-specific loss of <i>Srf</i> resulted in severe albuminuria and foot process effacement, and defects in cell adhesion and spreading, along with decreased <i>β</i>₁ integrin expression. Epsins play an indispensable role in maintaining properly functioning podocytes through the regulation of Cdc42 and SRF-dependent <i>β</i>₁ integrin expression.