Murine Epsins Play An Integral Role In Podocyte Function

Background Epsins, a family of evolutionarily conserved membrane proteins, play an essential role in endocytosis and signaling in podocytes.Methods Podocyte-specific Epn1, Epn2, Epn3 triple-knockout mice were generated to examine downstream regulation of serum response factor (SRF) by cell division control protein 42 homolog (Cdc42).Results Podocyte-specific loss of epsins resulted in increased albuminuria and foot process effacement. Primary podocytes isolated fromthese knockoutmice exhibited abnormalities in cell adhesion and spreading, whichmay be attributed to reduced activation of cell division control protein Cdc42 and SRF, resulting in diminished beta(1) integrin expression. In addition, podocyte-specific loss of Srf resulted in severe albuminuria and foot process effacement, and defects in cell adhesion and spreading, along with decreased b1 integrin expression.Conclusions Epsins play an indispensable role in maintaining properly functioning podocytes through the regulation of Cdc42 and SRF-dependent b1 integrin expression.