Kidney international · 2025
The kidney slit diaphragm resembles a fishnet.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Birtasu Alexandra N, Wieland Konstantin, Ermel Utz H, Arghittu Serena M, Manger Sina, Kocylowski Maciej K, Fakler Bernd, Scheffer Margot P, Covino Roberto, Grahammer Florian, Frangakis Achilleas S
Аннотация
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.
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.