ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2012
Trk activation of the ERK1/2 kinase pathway stimulates intermediate chain phosphorylation and recruits cytoplasmic dynein to signaling endosomes for retrograde axonal transport.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
57 citing papers in PubMed, 101 citations in OpenAlex.
- Molecular architects of memory: BDNF/TrkB signaling and trafficking in neuronal plasticity and memory.Molecular psychiatry · 2026Review
- The neuropathy-causingbioRxiv : the preprint server for biology · 2026Article
- Impaired BDNF-TrkB trafficking and signalling in Down syndrome basal forebrain neurons.Cell death & disease · 2026Article
- Ciliary neurotrophic factor slows axonal transport of signalling endosomes.Brain communications · 2026Article
- Disruption of axonal transport in Parkinson's disease: the role of pathological α-Syn and AMPK/p38 MAPK signaling.NPJ Parkinson's disease · 2025Article
- Opposing roles for GSK3β and ERK1-dependent phosphorylation of huntingtin during neuronal dysfunction and cell death in Huntington's disease.Cell death & disease · 2025Article
- Unveiling the role of erinacines in the neuroprotective effects ofFrontiers in pharmacology · 2025Review
- Boosting BDNF in muscle rescues impaired axonal transport in a mouse model of DI-CMTC peripheral neuropathy.Neurobiology of disease · 2024Article
- Boosting BDNF in muscle rescues impaired axonal transport in a mouse model of DI-CMTC peripheral neuropathy.bioRxiv : the preprint server for biology · 2024Article
- Docking protein 6 (DOK6) selectively docks the neurotrophic signaling transduction to restrain peripheral neuropathy.Signal transduction and targeted therapy · 2024Article
- Article
- c-Abl Tyrosine Kinase Is Required for BDNF-Induced Dendritic Branching and Growth.International journal of molecular sciences · 2023Article
- Spatial regulation of endosomes in growing dendrites.Developmental biology · 2022Review
- Axonal transport of late endosomes and amphisomes is selectively modulated by local CaScience advances · 2022Article
- Long-distance regressive signaling in neural development and disease.Wiley interdisciplinary reviews. Developmental biology · 2021Review
- Engagement of Neurotropic Viruses in Fast Axonal Transport: Mechanisms, Potential Role of Host Kinases and Implications for Neuronal Dysfunction.Frontiers in cellular neuroscience · 2021Article
- IGF1R regulates retrograde axonal transport of signalling endosomes in motor neurons.EMBO reports · 2020Article
- Axonal transport and neurological disease.Nature reviews. Neurology · 2019Review
- SIPA1L2 controls trafficking and local signaling of TrkB-containing amphisomes at presynaptic terminals.Nature communications · 2019Article
- Lysosome trafficking and signaling in health and neurodegenerative diseases.Neurobiology of disease · 2019Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 4 institutions in 1 country.
Funding
Abstract
The retrograde transport of Trk-containing endosomes from the axon to the cell body by cytoplasmic dynein is necessary for axonal and neuronal survival. We investigated the recruitment of dynein to signaling endosomes in rat embryonic neurons and PC12 cells. We identified a novel phosphoserine on the dynein intermediate chains (ICs), and we observed a time-dependent neurotrophin-stimulated increase in intermediate chain phosphorylation on this site in both cell types. Pharmacological studies, overexpression of constitutively active MAP kinase kinase, and an in vitro assay with recombinant proteins demonstrated that the intermediate chains are phosphorylated by the MAP kinase ERK1/2, extracellular signal-regulated kinase, a major downstream effector of Trk. Live cell imaging with fluorescently tagged IC mutants demonstrated that the dephosphomimic mutants had significantly reduced colocalization with Trk and Rab7, but not a mitochondrial marker. The phosphorylated intermediate chains were enriched on immunoaffinity-purified Trk-containing organelles. Inhibition of ERK reduced the amount of phospho-IC and the total amount of dynein that copurified with the signaling endosomes. In addition, inhibition of ERK1/2 reduced the motility of Rab7- and TrkB-containing endosomes and the extent of their colocalization with dynein in axons. NGF-dependent survival of sympathetic neurons was significantly reduced by the overexpression of the dephosphomimic mutant IC-1B-S80A, but not WT IC-1B, further demonstrating the functional significance of phosphorylation on this site. These results demonstrate that neurotrophin binding to Trk initiates the recruitment of cytoplasmic dynein to signaling endosomes through ERK1/2 phosphorylation of intermediate chains for their subsequent retrograde transport in axons.
Indexed as
Identifiers
What OpenQuestion holds
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.