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Cited by 32Renal Diseases and GlomerulopathiesAdvanced Electron Microscopy Techniques and ApplicationsCell Adhesion Molecules Research

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The kidney slit diaphragm resembles a fishnet

Open access
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.·2025·Kidney International
DOI 10.1016/j.kint.2025.08.028

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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.

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Metadata

Authors
Birtasu, A. N., Wieland, K., Ermel, U. H., Arghittu, S. M., Manger, S., Kocylowski, M. K., Fakler, B., Scheffer, M. P., Covino, R., Grahammer, F., & Frangakis, A. S.
Affiliations
  • Goethe University Frankfurt (DE)
  • Frankfurt Institute for Advanced Studies (DE)
  • University of Freiburg (DE)
  • University Medical Center Hamburg-Eppendorf (DE)
Corresponding author
Frangakis, Achilleas S.
ORCID
Venue
Kidney International
Publisher
Elsevier BV
Published
2025-12
Volume
108
Issue
6
Pages
1045-1056
ISSN
0085-2538 (ISSN-L)
DOI
10.1016/j.kint.2025.08.028
OpenAlex
W4414523045
Cited by
32
References
1
Citations by year
2026: 21 · 2025: 8
FWCI
20.33
Type
journal article
Language
en
Open access
Licence
Locations
  • Kidney International (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • FreiDok plus (Universitätsbibliothek Freiburg) (submittedVersion)
  • Publication Server of Goethe University Frankfurt am Main (Goethe University Frankfurt) (submittedVersion, cc-by-nc-nd)
  • Publication Server of Goethe University Frankfurt am Main (Goethe University Frankfurt) (submittedVersion, cc-by)
  • MPG.PuRe (Max Planck Society) (submittedVersion, other-oa)
Funders
  • DFG
  • Gauss Centre for Supercomputing (FR 1653/13-1, TRR-422, CRC 1192, FR 1653/14-1, GR3933/1-1, GRK 2566/1)
  • Universitätsklinikum Hamburg-Eppendorf
  • Goethe-Universität Frankfurt am Main
  • University of Washington
  • Frankfurt Institute for Advanced Studies
  • Albert-Ludwigs-Universität Freiburg
  • Australian Speleological Federation
  • School of Medicine, Washington University in St. Louis
Topics
  • Health Sciences › Medicine › Nephrology › Renal Diseases and Glomerulopathies
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Structural Biology › Advanced Electron Microscopy Techniques and Applications
  • Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
Keywords
slit diaphragm, glomerular filtration barrier, nephrin, Neph1, cell-cell contact, adhesion molecules, cryo-electron tomography, molecular dynamics simulation, glomerular ultrastructure
MeSH terms
Animals, Intercellular Junctions, Kidney Glomerulus, Membrane Proteins, Mice, Inbred C57BL, Cryoelectron Microscopy, Podocytes, Mice, Electron Microscope Tomography, Molecular Dynamics Simulation, Glomerular Filtration Barrier

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