CD2-associated protein participates in podocyte apoptosis via PI3K/Akt signaling pathway

CD2-associated protein is one of the most important slit diaphragm proteins in maintaining podocyte integrity and reducing proteinuria. In the last 15 years, progressive researches have shown that CD2AP serves as an adaptor protein, plays essential roles in the podocyte cytoskeletal structure and signaling from the extracellular SD to the intracellular dynamic actin cytoskeleton. CD2AP deficient or transcript abnormality would lead to podocyte failure and proteinuric glomerular diseases. In this study, we demonstrate that CD2AP and p85 regulatory subunit of phosphoinositide 3-OH kinase (PI3K), recruit PI3K to the plasma membrane, and stimulate PI3K-dependent AKT signaling in podocytes the CD2AP-mediated AKT activity can regulate complex biological programs. PAN reduces Akt phosphorylation levels of GSK3β, LY294002 can promote podocyte apoptosis induced by PAN. Our findings suggest that the activation of PI3K/AKT signaling represents an essential component to maintain the functional integrity of podocytes. And PI3K/Akt signaling pathway play an important role in podocyte apoptosis.