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bioRxiv · 10.1101/2025.09.24.678239

The native human glomerulus features a slit diaphragmresembling a densely interwoven fishnet

Frangakis, A. S.·Moser, D.·Birtasu, A. N.·Skaer, L.·Roth, P.·Rehm, L.·Wenzel, M.·Koellermann, J.·Mantanya, M. S.·Chun, F.·Frangakis, M.
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Abstract

The slit diaphragm (SD), a core element of the glomerular filtration barrier, is essential for renal filtration and disrupted in all forms of glomerulopathy. Using cryo-electron tomography of human kidney tissue, we resolved the near-native SD architecture at unprecedented resolution. The SD comprises crisscrossing strands intersecting at [~]90{degrees}, forming a fishnet-like lattice across the [~]44 nm space between podocyte foot processes. An atomic model based on the Nephrin-Neph1 heterodimer reveals [~]9 nm spacing in humans, compared with 12.3 nm in mice and 15 nm in Drosophila. Our data establish the SD as a conserved fishnet-like assembly from invertebrates to mammals, with the tighter human lattice likely conferring enhanced permselectivity.

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Frangakis, A. S., Moser, D., Birtasu, A. N., Skaer, L., Roth, P., Rehm, L., Wenzel, M., Koellermann, J., Mantanya, M. S., Chun, F., Frangakis, M.. 2025-09-26. The native human glomerulus features a slit diaphragmresembling a densely interwoven fishnet. https://doi.org/10.1101/2025.09.24.678239

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