The kidney slit diaphragm resembles a fishnet
Year: 2025
Type: article
Abstract: INTRODUCTION: 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. METHODS: Here, we use cryo-electron tomography of vitreous lamellae from high pressure frozen wild-type C57BL/6J native mouse glomeruli. RESULTS: 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. CONCLUSIONS: The molecular architecture of the murine slit diaphragm provides a mechanistic framework for comprehending kidney cell-cell junctions with immediate implications in disease.
Source: Kidney International
Language: English
Subfield: Nephrology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $3,500
Funders: University of Washington, Deutsche Forschungsgemeinschaft, Albert-Ludwigs-Universität Freiburg, Goethe-Universität Frankfurt am Main, Gauss Centre for Supercomputing, Australian Speleological Federation, Washington University School of Medicine in St. Louis, Universitätsklinikum Hamburg-Eppendorf, Frankfurt Institute for Advanced Studies
OpenAlex ID: W4414523045