ArticleThe EMBO journal2009
NRH2 is a trafficking switch to regulate sortilin localization and permit proneurotrophin-induced cell death.
Article in The EMBO journal, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 47 citations in OpenAlex.
- A Novel BIRC6 Variant Impairs Apoptotic Regulation in Familial Premature Ovarian Insufficiency: Functional Validation in a CRISPR/Cas9 Zebrafish Model.Reproductive sciences (Thousand Oaks, Calif.) · 2026Article
- Plasma and CSF Amyloid-β42 Predict Plasma Sortilin, Which Influences Cognitive Impairment via Mediation of Whole-Brain Volume: A 12-Month Longitudinal Study Across the Alzheimer's Disease Spectrum.Journal of molecular neuroscience : MN · 2025Article
- The luminal domain ofFrontiers in parasitology · 2023Article
- Confronting the loss of trophic support.Frontiers in molecular neuroscience · 2023Article
- Sortilin enhances secretion of apolipoprotein(a) through effects on apolipoprotein B secretion and promotes uptake of lipoprotein(a).Journal of lipid research · 2022Article
- Diagnostic and Therapeutic Implications of Sortilin Expressed on the Surface of Bladder Carcinoma Cells.Iranian journal of pathology · 2022Article
- Significance of Endocan Expression in Various Types of Epithelial Ovarian Tumors.Iranian journal of pathology · 2022Article
- Nradd Acts as a Negative Feedback Regulator of Wnt/β-Catenin Signaling and Promotes Apoptosis.Biomolecules · 2021Article
- Valproic acid upregulates the expression of the p75NTR/sortilin receptor complex to induce neuronal apoptosis.Apoptosis : an international journal on programmed cell death · 2020Article
- PROneurotrophins and CONSequences.Molecular neurobiology · 2018Review
- Sortilin limits EGFR signaling by promoting its internalization in lung cancer.Nature communications · 2017Article
- Detection of p75NTR Trimers: Implications for Receptor Stoichiometry and Activation.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2015Article
- Article
- Sortilin and lipoprotein metabolism: making sense out of complexity.Current opinion in lipidology · 2014Review
- Heterodimerization of p45-p75 modulates p75 signaling: structural basis and mechanism of action.PLoS biology · 2014Article
- Interleukin-1β enhances neuronal vulnerability to proNGF-mediated apoptosis by increasing surface expression of p75(NTR) and sortillin.Neuroscience · 2014Article
- P45 forms a complex with FADD and promotes neuronal cell survival following spinal cord injury.PloS one · 2013Article
- Hippocampal proNGF signaling pathways and β-amyloid levels in mild cognitive impairment and Alzheimer disease.Journal of neuropathology and experimental neurology · 2012Article
- Neurotrophic actions initiated by proNGF in adult sensory neurons may require peri-somatic glia to drive local cleavage to NGF.Journal of neurochemistry · 2012Article
- Association between p75 neurotrophin receptor gene expression and cell apoptosis in tissues surrounding hematomas in rat models of intracerebral hemorrhage.Neural regeneration research · 2012Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Proneurotrophins mediate neuronal apoptosis using a dual receptor complex of sortilin and p75(NTR). Although p75(NTR) is highly expressed on the plasma membrane and accessible to proneurotrophin ligands, sortilin is primarily localized to intracellular membranes, limiting the formation of a cell surface co-receptor complex. Here, we show that the mammalian p75(NTR) homologue NRH2 critically regulates the expression of sortilin on the neuronal cell surface and promotes p75(NTR) and sortilin receptor complex formation, rendering cells responsive to proneurotrophins. This is accomplished by interactions between the cytoplasmic domains of NRH2 and sortilin that impair lysosomal degradation of sortilin. In proneurotrophin-responsive neurons, acute silencing of endogenous NRH2 significantly reduces cell surface-expressed sortilin and abolishes proneurotrophin-induced neuronal death. Thus, these data suggest that NRH2 acts as a trafficking switch to impair lysosomal-dependant sortilin degradation and to redistribute sortilin to the cell surface, rendering p75(NTR)-expressing cells susceptible to proneurotrophin-induced death.
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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.