The kidney slit diaphragm resembles a fishnet.

Abstract

An essential component of the kidney filtration barrier, the slit diaphragm, is a specialized cell-cell junction composed of the cell adhesion molecules Nephrin and Neph1. Here, we use cryo-electron tomography of vitreous lamellae from high pressure frozen wild-type C57BL/6J native mouse glomeruli. The cryo-electron tomograms show that the slit diaphragm resembles a fishnet-like architecture. After sub-tomogram averaging and molecular dynamics flexible fitting of Nephrin and Neph1, the resulting molecular model of the slit diaphragm reveals a criss-cross arrangement of these cell adhesion molecules with multiple homo- and hetero-philic interactions. This renders the slit diaphragm as a single- or a multi-layer fishnet, quasi-crystalline, sheet-like molecular polymer that can provide both stability and flexibility to compensate for mechanical forces. The molecular architecture of the murine slit diaphragm provides a mechanistic framework for comprehending kidney cell-cell junctions with immediate implications in disease.