ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2013
Defective axonal transport of Rab7 GTPase results in dysregulated trophic signaling.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.
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Who cites it
66 citing papers in PubMed, 103 citations in OpenAlex.
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- Maspardin/SPG21 controls lysosome motility and TFEB phosphorylation through RAB7 positioning.The Journal of cell biology · 2026Article
- Increased Neuronal Expression of the Early Endosomal Adaptor APPL1 Replicates Alzheimer's Disease-Related Endosomal and Synaptic Dysfunction with Cholinergic Neurodegeneration.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- Axonal transport of CHMP2b is regulated by kinesin-binding protein and disrupted by CHMP2bLife science alliance · 2025Article
- ARF4-mediated retrograde trafficking as a driver of chemoresistance in glioblastoma.Neuro-oncology · 2024Article
- Nerve Growth Factor Signaling Modulates the Expression of Glutaminase in Dorsal Root Ganglion Neurons during Peripheral Inflammation.International journal of molecular sciences · 2024Article
- Mitochondrial DNA replication stress triggers a pro-inflammatory endosomal pathway of nucleoid disposal.Nature cell biology · 2024Article
- Misregulation of mitochondria-lysosome contact dynamics in Charcot-Marie-Tooth Type 2B disease Rab7 mutant sensory peripheral neurons.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Regulation of Endosomal Trafficking by Rab7 and Its Effectors in Neurons: Clues from Charcot-Marie-Tooth 2B Disease.Biomolecules · 2023Review
- Disruption of axonal transport in neurodegeneration.The Journal of clinical investigation · 2023Review
- Human TrkAR649W mutation impairs nociception, sweating and cognitive abilities: a mouse model of HSAN IV.Human molecular genetics · 2023Article
- HTT (huntingtin) and RAB7 co-migrate retrogradely on a signaling LAMP1-containing late endosome during axonal injury.Autophagy · 2023Article
- Overexpression of alpha synuclein disrupts APP and Endolysosomal axonal trafficking in a mouse model of synucleinopathy.Neurobiology of disease · 2023Article
- Differential axonal trafficking of Neuropeptide Y-, LAMP1-, and RAB7-tagged organelles in vivo.eLife · 2022Article
- Mitochondria dysfunction in Charcot Marie Tooth 2B Peripheral Sensory Neuropathy.Communications biology · 2022Article
- Genetic pain loss disorders.Nature reviews. Disease primers · 2022Review
- Mitochondria-lysosome contact site dynamics and misregulation in neurodegenerative diseases.Trends in neurosciences · 2022Review
- Enhancing autophagy maturation with CCZ1-MON1A complex alleviates neuropathology and memory defects in Alzheimer disease models.Theranostics · 2022Article
- Article
6 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
Abstract
Retrograde trophic signaling of nerve growth factor (NGF) supports neuronal survival and differentiation. Dysregulated trophic signaling could lead to various neurological disorders. Charcot-Marie-Tooth type 2B (CMT2B) is one of the most common inherited peripheral neuropathies characterized by severe terminal axonal loss. Genetic analysis of human CMT2B patients has revealed four missense point mutations in Rab7, a small GTPase that regulates late endosomal/lysosomal pathways, but the exact pathological mechanism remains poorly understood. Here, we show that these Rab7 mutants dysregulated axonal transport and diminished the retrograde signaling of NGF and its TrkA receptor. We found that all CMT2B Rab7 mutants were transported significantly faster than Rab7(wt) in the anterograde direction, accompanied with an increased percentile of anterograde Rab7-vesicles within axons of rat E15.5 dorsal root ganglion (DRG) neurons. In PC12M cells, the CMT2B Rab7 mutants drastically reduced the level of surface TrkA and NGF binding, presumably by premature degradation of TrkA. On the other hand, siRNA knock-down of endogenous Rab7 led to the appearance of large TrkA puncta in enlarged Rab5-early endosomes within the cytoplasm, suggesting delayed TrkA degradation. We also show that CMT2B Rab7 mutants markedly impaired NGF-induced Erk1/2 activation and differentiation in PC12M cells. Further analysis revealed that CMT2B Rab7 mutants caused axonal degeneration in rat E15.5 DRG neurons. We propose that Rab7 mutants induce premature degradation of retrograde NGF-TrkA trophic signaling, which may potentially contribute to the CMT2B disease.
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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.