The role of the tricellular junction protein ILDR2 in glomerulopathies: Expression patterns and functional insights

Siegerist, Florian and Kliewe, Felix and Hammer, Elke and Schakau, Paul and Soh, Joanne Ern Chi and Weber, Claudia and Lindenmeyer, Maja and Reichelt-Wurm, Simone and Drenic, Vedran and Chatziantoniou, Christos and Chadjichristos, Christos E. and Zhang, Yiying and Simm, Stefan and Banas, Miriam C. and Nauck, Matthias and Völker, Uwe and Endlich, Nicole (2024) The role of the tricellular junction protein ILDR2 in glomerulopathies: Expression patterns and functional insights. ISCIENCE, 27 (12): 111329. ISSN 2589-0042

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Abstract

The tricellular tight junctions are crucial for the regulation of paracellular flux at tricellular junctions, where tricellulin (MARVELD2) and angulins (ILDR1, ILDR2, or LSR) are localized. The role of ILDR2 in podocytes, specialized epithelial cells in the kidney, is still unknown. We investigated the role of ILDR2 in glomeruli and its influence on blood filtration. Western blots, single-cell RNA sequencing (scRNA-seq), and superresolution microscopy showed a strong expression of ILDR2 in podocytes that colocalized with the podocytespecific claudin CLDN5. Co-immunoprecipitation revealed that ILDR2 interacts with CLDN5. In glomerulopathies, induced by nephrotoxic serum and by desoxycorticosterone acetate (DOCA)-salt heminephrectomy, ILDR2 was strongly up-regulated. Furthermore, Ildr2 knockout mice exhibited glomerular hypertrophy and decreased podocyte density. However, they did not develop effacement of podocyte foot processes or proteinuria. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) proteomic analysis of isolated glomeruli showed an increase in matrix proteins, such as fibronectin and collagens. This suggests a protective role of ILDR2 in glomerulopathies.

Item Type: Article
Uncontrolled Keywords: TIGHT JUNCTION; BARRIER; Highlights; Natural sciences; Biological sciences; Physiology; Cellular physiology
Subjects: 600 Technology > 610 Medical sciences Medicine
Divisions: Medicine > Abteilung für Nephrologie
Depositing User: Dr. Gernot Deinzer
Date Deposited: 14 Jan 2026 09:23
Last Modified: 14 Jan 2026 09:23
URI: https://pred.uni-regensburg.de/id/eprint/65339

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