ArticleNature communications2017
Low pH-induced conformational change and dimerization of sortilin triggers endocytosed ligand release.
Article in Nature communications, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.
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Who cites it
20 citing papers in PubMed, 1 synthesis or guideline pooled it, 51 citations in OpenAlex.
- Finding memo: versatile interactions of the VPS10p-Domain receptors in Alzheimer's disease.Molecular neurodegeneration · 2022Pooled it
- Visualization of membrane-stabilized SorCS2Journal of structural biology: X · 2026Article
- Rational Design of Peptide Binders Targeting Prominin‑1 and Sortilin for Molecular Sensing Applications.ACS omega · 2026Article
- Mindin-mediated αM-integrin endocytosis activates STAT3 to maintain keratinocyte stemness.Cell communication and signaling : CCS · 2026Article
- Molecular recognition of thyroglobulin by sortilin.Nature communications · 2026Article
- Impaired chaperone-mediated autophagy leads to abnormal SORT1 (sortilin 1) turnover and CES1-dependent triglyceride hydrolysis.Autophagy · 2025Article
- Article
- TheProceedings of the National Academy of Sciences of the United States of America · 2024Article
- Rational design and topochemical synthesis of polymorphs of a polymer.Chemical science · 2023Article
- Neurotensin and Alcohol Use Disorders: Towards a Pharmacological Treatment.International journal of molecular sciences · 2023Review
- Dimerization of the Alzheimer's disease pathogenic receptor SORLA regulates its association with retromer.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- A lysosomal biogenesis map reveals the cargo spectrum of yeast vacuolar protein targeting pathways.The Journal of cell biology · 2022Article
- A study on the secondary structure of the metalloregulatory protein CueR: effect of pH, metal ions and DNA.European biophysics journal : EBJ · 2021Article
- An Allosteric Binding Site on Sortilin Regulates the Trafficking of VLDL, PCSK9, and LDLR in Hepatocytes.Biochemistry · 2020Article
- Structural Perspectives on Extracellular Recognition and Conformational Changes of Several Type-I Transmembrane Receptors.Frontiers in molecular biosciences · 2020Review
- Mutant Huntingtin Affects Diabetes and Alzheimer's Markers in Human and Cell Models of Huntington's Disease.Cells · 2019Article
- De novo design of tunable, pH-driven conformational changes.Science (New York, N.Y.) · 2019Article
- An alternative transcript of the Alzheimer's disease risk gene SORL1 encodes a truncated receptor.Neurobiology of aging · 2018Article
- Structural insights into SorCS2-Nerve Growth Factor complex formation.Nature communications · 2018Article
- The Involvement of Sortilin/NTSR3 in Depression as the Progenitor of Spadin and Its Role in the Membrane Expression of TREK-1.Frontiers in pharmacology · 2018Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Low pH-induced ligand release and receptor recycling are important steps for endocytosis. The transmembrane protein sortilin, a β-propeller containing endocytosis receptor, internalizes a diverse set of ligands with roles in cell differentiation and homeostasis. The molecular mechanisms of pH-mediated ligand release and sortilin recycling are unresolved. Here we present crystal structures that show the sortilin luminal segment (s-sortilin) undergoes a conformational change and dimerizes at low pH. The conformational change, within all three sortilin luminal domains, provides an altered surface and the dimers sterically shield a large interface while bringing the two s-sortilin C-termini into close proximity. Biophysical and cell-based assays show that members of two different ligand families, (pro)neurotrophins and neurotensin, preferentially bind the sortilin monomer. This indicates that sortilin dimerization and conformational change discharges ligands and triggers recycling. More generally, this work may reveal a double mechanism for low pH-induced ligand release by endocytosis receptors.
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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.