ArticleMolecular biology of the cell2009
Analysis of uromodulin polymerization provides new insights into the mechanisms regulating ZP domain-mediated protein assembly.
Article in Molecular biology of the cell, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers, 1 of them a synthesis that pooled it.
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Who cites it
54 citing papers in PubMed, 1 synthesis or guideline pooled it, 91 citations in OpenAlex.
- Common variants in UMOD associate with urinary uromodulin levels: a meta-analysis.Journal of the American Society of Nephrology : JASN · 2014Pooled it
- Human Tamm-Horsfall protein as a novel antitumor therapy for triple negative breast cancer and other solid tumors.Scientific reports · 2026Article
- Zona pellucida-inspired smart viral vectors: a biomimetic platform for multi-modal immune evasion and triple-stimuli responsive gene delivery.Frontiers in bioengineering and biotechnology · 2026Article
- Endocrine regulation of uromodulin in aging.Frontiers in endocrinology · 2026Review
- Mutations in UMOD Contribute to the Pathogenesis of ADTKD-UMOD by Influencing the Function of Complement Factor H.Journal of cellular and molecular medicine · 2026Article
- Early renal response to long-term salt loading: mitochondrial dysfunction, ER stress, and uromodulin accumulation in the kidney medulla.American journal of physiology. Renal physiology · 2025Article
- Microvilli control the morphogenesis of the tectorial membrane extracellular matrix.Developmental cell · 2025Article
- Disrupted uromodulin trafficking is rescued by targeting TMED cargo receptors.The Journal of clinical investigation · 2024Article
- Advances in uromodulin biology and potential clinical applications.Nature reviews. Nephrology · 2024Review
- Article
- Microvilli regulate the release modes of alpha-tectorin to organize the domain-specific matrix architecture of the tectorial membrane.bioRxiv : the preprint server for biology · 2024Article
- Unveiling the Hidden Power of Uromodulin: A Promising Potential Biomarker for Kidney Diseases.Diagnostics (Basel, Switzerland) · 2023Review
- Zona Pellucida like Domain Protein 1 (ZPLD1) Polymerization Is Regulated by Two Distinguished Hydrophobic Motifs.International journal of molecular sciences · 2022Article
- Evolving Concepts in Uromodulin Biology, Physiology, and Its Role in Disease: a Tale of Two Forms.Hypertension (Dallas, Tex. : 1979) · 2022Review
- Role of Uromodulin in Salt-Sensitive Hypertension.Hypertension (Dallas, Tex. : 1979) · 2022Review
- Article
- Uromodulin Regulates Murine Aquaporin-2 Activity via Thick Ascending Limb-Collecting Duct Cross-Talk during Water Deprivation.International journal of molecular sciences · 2022Article
- Genome-wide studies reveal factors associated with circulating uromodulin and its relationships to complex diseases.JCI insight · 2022Article
- The kidney releases a nonpolymerizing form of uromodulin in the urine and circulation that retains the external hydrophobic patch domain.American journal of physiology. Renal physiology · 2022Article
- Zona Pellucida Genes and Proteins: Essential Players in Mammalian Oogenesis and Fertility.Genes · 2021Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Uromodulin is the most abundant protein secreted in urine, in which it is found as a high-molecular-weight polymer. Polymerization occurs via its zona pellucida (ZP) domain, a conserved module shared by many extracellular eukaryotic proteins that are able to assemble into matrices. In this work, we identified two motifs in uromodulin, mapping in the linker region of the ZP domain and in between protein cleavage and glycosylphosphatidylinositol (GPI)-anchoring sites, which regulate its polymerization. Indeed, mutations in either module led to premature intracellular polymerization of a soluble uromodulin isoform, demonstrating the inhibitory role of these motifs for ZP domain-mediated protein assembly. Proteolytic cleavage separating the external motif from the mature monomer is necessary to release the inhibitory function and allow protein polymerization. Moreover, we report absent or abnormal assembly into filaments of GPI-anchored uromodulin mutated in either the internal or the external motif. This effect is due to altered processing on the plasma membrane, demonstrating that the presence of the two modules has not only an inhibitory function but also can positively regulate protein polymerization. Our data expand previous knowledge on the control of ZP domain function and suggest a common mechanism regulating polymerization of ZP domain proteins.
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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.