Phosphorylation of key podocyte proteins and the association with proteinuric kidney disease.

Abstract

Podocyte dysfunction contributes to proteinuric chronic kidney disease. A number of key proteins are essential for podocyte function, including nephrin, podocin, CD2-associated protein (CD2AP), synaptopodin, and α-actinin-4 (ACTN4). Although most of these proteins were first identified through genetic studies associated with human kidney disease, subsequent studies have identified phosphorylation of these proteins as an important posttranslational event that regulates their function. In this review, a brief overview of the function of these key podocyte proteins is provided. Second, the role of phosphorylation in regulating the function of these proteins is described. Third, the association between these phosphorylation pathways and kidney disease is reviewed. Finally, challenges and future directions in studying phosphorylation are discussed. Better characterization of these phosphorylation pathways and others yet to be discovered holds promise for translating this knowledge into new therapies for patients with proteinuric chronic kidney disease.