ArticleScience advances2022
Calcineurin and huntingtin form a calcium-sensing machinery that directs neurotrophic signals to the nucleus.
Article in Science advances, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
What it found
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The trial behind it
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Who cites it
12 citing papers in PubMed.
- Molecular architects of memory: BDNF/TrkB signaling and trafficking in neuronal plasticity and memory.Molecular psychiatry · 2026Review
- Axonopathy: mechanisms and potential therapeutic targets for neurodegenerative diseases.Translational neurodegeneration · 2026Review
- Ciliary neurotrophic factor slows axonal transport of signalling endosomes.Brain communications · 2026Article
- Mycobacterium tuberculosis protein Rv2652c enhances intracellular survival by inhibiting host immune responses.Immunity, inflammation and disease · 2024Article
- Huntingtin contains an ubiquitin-binding domain and regulates lysosomal targeting of mitochondrial and RNA-binding proteins.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Presynaptic perspective: Axonal transport defects in neurodevelopmental disorders.The Journal of cell biology · 2024Review
- Characterization of Retinal VIP-Amacrine Cell Development During the Critical Period.Cellular and molecular neurobiology · 2024Article
- PLC-γ-CaFrontiers in molecular neuroscience · 2024Article
- Review
- Article
- A cellular atlas of calcineurin signaling.Biochimica et biophysica acta. Molecular cell research · 2023Review
- Selective motor activation in organelle transport along axons.Nature reviews. Molecular cell biology · 2022Review
Corrections and comments
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Authors and funding
5 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
When a neurotrophin binds at the presynapse, it sends survival signals all the way to the nucleus on signaling endosomes. These endosomes fuel their own journey with on-board glycolysis—but how is that journey initiated and maintained? Using microfluidic devices and mice, we find that the calcium released upon brain-derived neurotrophic factor (BDNF) binding to its receptor, tropomyosin receptor kinase B (TrkB), is sensed by calcineurin on the cytosolic face of the endosome. Calcineurin dephosphorylates huntingtin, the BDNF scaffold, which sets the endosome moving in a retrograde direction. In an in vitro reconstituted microtubule transport system, controlled calcium uncaging prompts purified vesicles to move to the microtubule minus end. We observed similar retrograde waves of TrkA- and epidermal growth factor receptor (EGFR)-bearing endosomes. Signaling endosomes in neurons thus carry not only their own fuel, but their own navigational system.
Identifiers
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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.