ArticleNature2006
Nck adaptor proteins link nephrin to the actin cytoskeleton of kidney podocytes.
Article in Nature, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 246 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
246 citing papers in PubMed, 1 synthesis or guideline pooled it, 476 citations in OpenAlex.
- Genetic and environmental factors associated with alteration of filtration slit proteins and their functions: a scoping review.Frontiers in nephrology · 2025Pooled it
- Towards an integrative structural model of the fishnet slit diaphragm: Understanding its physiology through proteomics and structural insight.Pflugers Archiv : European journal of physiology · 2026Review
- Reduced podocyte stiffness is a feature of proteinuric kidney disease.Kidney international · 2026Article
- Article
- Mapping of PTP1B, TCPTP, SHP2, and Putative Substrates Reveals Novel Networks in Glomerular Podocytes.Journal of cellular physiology · 2026Article
- Emerging genetic mechanisms of glomerular proteinuria: a podocyte-centered multi-layer network perspective.Frontiers in genetics · 2026Review
- Real-world pharmacovigilance and molecular mechanisms of fruquintinib: SRC and STAT3 as potential off-target mediators of proteinuria.Frontiers in pharmacology · 2026Article
- Differential Expression of Disulfidptosis-Related Genes in Spinal Cord Injury and Their Role in the Immune Microenvironment.Molecular neurobiology · 2025Article
- The intelligent podocyte: sensing and responding to a complex microenvironment.Nature reviews. Nephrology · 2025Review
- Reduced nephrin tyrosine phosphorylation impairs podocyte force transmission and accelerates detachment in disease.iScience · 2025Article
- Revisiting nephrin signaling and its specialized effects on the uniquely adaptable podocyte.The Biochemical journal · 2025Review
- TccP4: a novel effector identified in theMicrobiology spectrum · 2025Article
- Phenotypic quantification of Nphs1-deficient mice.Journal of nephrology · 2025Article
- Multi-condensate state as a functional strategy to optimize the cell signaling output.Nature communications · 2024Article
- Reduced Nephrin Tyrosine Phosphorylation Enhances Insulin Secretion and Increases Glucose Tolerance With Age.Endocrinology · 2024Article
- Contrasting consequences of podocyte insulin-like growth factor 1 receptor inhibition.iScience · 2024Article
- Multi-condensate state as a functional strategy to optimize the cell signaling output.bioRxiv : the preprint server for biology · 2024Article
- Phase separation-mediated biomolecular condensates and their relationship to tumor.Cell communication and signaling : CCS · 2024Review
- Liquid-liquid phase separation in Alzheimer's disease.Journal of molecular medicine (Berlin, Germany) · 2024Review
- Cytoskeleton Rearrangement in Podocytopathies: An Update.International journal of molecular sciences · 2024Review
186 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
Authors and funding
12 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The glomerular filtration barrier in the kidney is formed in part by a specialized intercellular junction known as the slit diaphragm, which connects adjacent actin-based foot processes of kidney epithelial cells (podocytes). Mutations affecting a number of slit diaphragm proteins, including nephrin (encoded by NPHS1), lead to renal disease owing to disruption of the filtration barrier and rearrangement of the actin cytoskeleton, although the molecular basis for this is unclear. Here we show that nephrin selectively binds the Src homology 2 (SH2)/SH3 domain-containing Nck adaptor proteins, which in turn control the podocyte cytoskeleton in vivo. The cytoplasmic tail of nephrin has multiple YDxV sites that form preferred binding motifs for the Nck SH2 domain once phosphorylated by Src-family kinases. We show that this Nck-nephrin interaction is required for nephrin-dependent actin reorganization. Selective deletion of Nck from podocytes of transgenic mice results in defects in the formation of foot processes and in congenital nephrotic syndrome. Together, these findings identify a physiological signalling pathway in which nephrin is linked through phosphotyrosine-based interactions to Nck adaptors, and thus to the underlying actin cytoskeleton in podocytes. Simple and widely expressed SH2/SH3 adaptor proteins can therefore direct the formation of a specialized cellular morphology in vivo.
Indexed as
Identifiers
What OpenQuestion holds
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.