ArticleThe Journal of biological chemistry2011
Precursor of brain-derived neurotrophic factor (proBDNF) forms a complex with Huntingtin-associated protein-1 (HAP1) and sortilin that modulates proBDNF trafficking, degradation, and processing.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers, 1 of them a synthesis that pooled it.
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Who cites it
41 citing papers in PubMed, 1 synthesis or guideline pooled it, 71 citations in OpenAlex.
- Finding memo: versatile interactions of the VPS10p-Domain receptors in Alzheimer's disease.Molecular neurodegeneration · 2022Pooled it
- Huntingtin polyglutamine expansions misdirect axonal transport by perturbing motor and adaptor recruitment.iScience · 2026Article
- Hippocampal Hap1 down-regulation impairs glucocorticoid receptor nuclear translocation and exacerbates Alzheimer's disease-related neuropathology in APP/PS1 mice.Zoological research · 2026Article
- Brain-Derived Neurotrophic Factor Trafficking via the Regulated Secretory Pathway: Mechanisms and Disease Implications.Molecular neurobiology · 2025Review
- Research advances in huntingtin-associated protein 1 and its application prospects in diseases.Frontiers in neuroscience · 2024Review
- Interaction of Brain-derived Neurotrophic Factor, Exercise, and Fear Extinction: Implications for Post-traumatic Stress Disorder.Current neuropharmacology · 2024Review
- Huntingtin-associated protein 1-associated intracellular trafficking in neurodegenerative diseases.Frontiers in aging neuroscience · 2023Review
- Sortilin deletion in the prefrontal cortex and hippocampus ameliorates depressive-like behaviors in mice via regulating ASM/ceramide signaling.Acta pharmacologica Sinica · 2022Article
- BDNF and Pro-BDNF in Amyotrophic Lateral Sclerosis: A New Perspective for Biomarkers of Neurodegeneration.Brain sciences · 2022Article
- The BDNF/TrkB Neurotrophin System in the Sensory Organs of Zebrafish.International journal of molecular sciences · 2022Review
- Uncovering a Genetic Polymorphism Located in Huntingtin Associated Protein 1 in Modulation of Central Pain Sensitization Signaling Pathways.Frontiers in neuroscience · 2022Article
- Dorsolateral Striatal proBDNF Improves Reversal Learning by Enhancing Coordination of Neural Activity in Rats.Molecular neurobiology · 2020Article
- Huntingtin-associated protein 1 plays an essential role in the pathogenesis of type 2 diabetes by regulating the translocation of GLUT4 in mouse adipocytes.BMJ open diabetes research & care · 2020Article
- Contribution of Neurotrophins to the Immune System Regulation and Possible Connection to Alcohol Addiction.Biology · 2020Review
- Huntingtin-Associated Protein 1 in Mouse Hypothalamus Stabilizes Glucocorticoid Receptor in Stress Response.Frontiers in cellular neuroscience · 2020Article
- The adaptor proteins HAP1a and GRIP1 collaborate to activate the kinesin-1 isoform KIF5C.Journal of cell science · 2019Article
- Knockout of p75 neurotrophin receptor attenuates the hyperphosphorylation of Tau in pR5 mouse model.Aging · 2019Article
- Furin promotes dendritic morphogenesis and learning and memory in transgenic mice.Cellular and molecular life sciences : CMLS · 2018Article
- Investigation of Mature BDNF and proBDNF Signaling in a Rat Photothrombotic Ischemic Model.Neurochemical research · 2018Article
- HAP1 Is Required for Endocytosis and Signalling of BDNF and Its Receptors in Neurons.Molecular neurobiology · 2018Article
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
proBDNF, a precursor of brain-derived neurotrophic factor (BDNF), is anterogradely transported and released from nerve terminals, but the mechanism underlying this process remains unclear. In this study, we report that proBDNF forms a complex with Huntingtin associated protein-1 (HAP1) and sortilin, which plays an important role in proBDNF intracellular trafficking and stabilization. The interaction of proBDNF with both HAP1A and sortilin in co-transfected HEK293 cells is confirmed by both fluorescence resonance energy transfer and co-immunoprecipitation. The frequent co-localization (>90%) of endogenous HAP1, sortilin, and proBDNF is also found in cultured cortical neurons. Mapping studies using GST pulldown and competition assays has defined the interacting region of HAP1 with proBDNF within amino acids 371-445 and the binding sequences of proBDNF to HAP1 between amino acids 65 and 90. Fluorescence recovery after photobleaching confirms the defective movement of proBDNF-containing vesicles in neurites of HAP1(-/-) neurons, which can be partially restored by reintroducing HAP1 cDNA into the neurons. However, the effect is significantly increased by simultaneously reintroducing both HAP1 and sortilin. proBDNF and HAP1 are highly co-localized with organelle markers for the Golgi network, microtubules, molecular motor, or endosomes in normal neurons, but this co-localization is reduced in HAP1(-/-) neurons. Co-immunoprecipitation and Western blot showed that sortilin stabilizes the proBDNF·HAP1 complex in co-transfected HEK293 cells, helping to prevent proBDNF degradation. Furthermore, the complex facilitates furin cleavage to release mature BDNF.
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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.