Molecular Structure-Function Relationship in the Slit Diaphragm

The past 5 years have witnessed an exponential increase in our understanding of the structure and function of the glomerular slit diaphragm. The identification of nephrin as the first transmembrane slit diaphragm protein was a watershed event in slit diaphragm biology. This article correlates some of the observations of the prenephrin era with more recent studies, and elaborates on the individual characteristics of each slit diaphragm protein. Recent studies on protein-protein interactions related to slit diaphragm permeability and cell signaling are elaborated, along with observations on their expression in human disease and experimental models of proteinuria. Developmental expression of components of the slit diaphragm in normal and knockout mice also is discussed. Finally, some areas of future investigation are proposed.