ArticleThe Journal of clinical investigation2021
Endoplasmic reticulum-associated degradation is required for nephrin maturation and kidney glomerular filtration function.
Article in The Journal of clinical investigation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 60 citations in OpenAlex.
- Comprehensive bioinformatics and experimental analysis of PPOX reveals its carcinogenic effect in clear cell renal cell carcinoma.Translational andrology and urology · 2026Article
- Functional rescue of a disease-linked ERAD pathway mutation via alternative splicing.The EMBO journal · 2026Article
- SEL1L-HRD1 ERAD-autophagy interplay maintains mitochondrial homeostasis in brown adipocytes.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Functional integrity of the SEL1L-HRD1 complex is critical for endoplasmic reticulum-associated degradation and organismal viability.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Structural basis and pathological implications of the dimeric OS9-SEL1L-HRD1 ERAD Core Complex.Nature communications · 2026Article
- Dihydromyricetin protects against cisplatin-induced renal injury and mitochondria-mediated apoptosis via the EGFR/HSP27/STAT3 signaling pathway.Renal failure · 2025Article
- MYC affects mitochondrial function in IgA nephropathy by promoting the degradation of MFN1 through HRD1.Immunologic research · 2025Article
- [Potential of early diagnosis and targeted therapy for Klotho protein in chronic kidney disease].Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2025Review
- A hypoxia-responsive tRNA-derived small RNA confers renal protection through RNA autophagy.Science (New York, N.Y.) · 2025Article
- SEL1L regulates ER homeostasis in Sertoli cells but is dispensable for their function.Molecular biology of the cell · 2025Article
- Endoplasmic reticulum (ER) protein degradation by ER-associated degradation and ER-phagy.Trends in cell biology · 2025Review
- Structural insights into the human HRD1 ubiquitin ligase complex.Nature communications · 2025Article
- SEL1L-HRD1-mediated ERAD in mammals.Nature cell biology · 2025Review
- Coordinated Role of Autophagy and ERAD in Maintaining Neuroendocrine Function by Preventing Prohormone Aggregation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
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- Anti-nephrin antibody: a potential biomarker of minimal change disease.Clinical kidney journal · 2025Article
- SA4503 Mitigates Adriamycin-Induced Nephropathy via Sigma-1 Receptor in Animal and Cell-Based Models.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Loss-of-function mutations of microRNA-142-3p promoteWorld journal of gastroenterology · 2025Article
- HNF-1β alleviates podocyte injury in lupus nephritis by maintaining endoplasmic reticulum homeostasis.Lupus science & medicine · 2024Article
Corrections and comments
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Authors and funding
24 authors at 6 institutions in 3 countries.
Funding
Abstract
Podocytes are key to the glomerular filtration barrier by forming a slit diaphragm between interdigitating foot processes; however, the molecular details and functional importance of protein folding and degradation in the ER remain unknown. Here, we show that the SEL1L-HRD1 protein complex of ER-associated degradation (ERAD) is required for slit diaphragm formation and glomerular filtration function. SEL1L-HRD1 ERAD is highly expressed in podocytes of both mouse and human kidneys. Mice with podocyte-specific Sel1L deficiency develop podocytopathy and severe congenital nephrotic syndrome with an impaired slit diaphragm shortly after weaning and die prematurely, with a median lifespan of approximately 3 months. We show mechanistically that nephrin, a type 1 membrane protein causally linked to congenital nephrotic syndrome, is an endogenous ERAD substrate. ERAD deficiency attenuated the maturation of nascent nephrin, leading to its retention in the ER. We also show that various autosomal-recessive nephrin disease mutants were highly unstable and broken down by SEL1L-HRD1 ERAD, which attenuated the pathogenicity of the mutants toward the WT allele. This study uncovers a critical role of SEL1L-HRD1 ERAD in glomerular filtration barrier function and provides insights into the pathogenesis associated with autosomal-recessive disease mutants.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.