ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2012
A model of toxic neuropathy in Drosophila reveals a role for MORN4 in promoting axonal degeneration.
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 51 papers.
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51 citing papers in PubMed, 75 citations in OpenAlex.
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- PDH Inhibition inBiomedicines · 2025Article
- A missense mutation in human INSC causes peripheral neuropathy.EMBO molecular medicine · 2024Article
- TgMORN2, a MORN Family Protein Involved in the Regulation of Endoplasmic Reticulum Stress inInternational journal of molecular sciences · 2023Article
- Review
- A nerve-wracking buzz: lessons fromFrontiers in aging neuroscience · 2023Review
- Mechanisms of Axon Growth and Regeneration: Moving between Development and Disease.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2022Article
- Nano-positioning and tubulin conformation contribute to axonal transport regulation of mitochondria along microtubules.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- The role of junctophilin proteins in cellular function.Physiological reviews · 2022Review
- Cellular Pathogenesis of Chemotherapy-Induced Peripheral Neuropathy: Insights FromFrontiers in pain research (Lausanne, Switzerland) · 2022Review
- Integrins protect sensory neurons in models of paclitaxel-induced peripheral sensory neuropathy.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
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- Experimental Model Systems for Understanding Human Axonal Injury Responses.International journal of molecular sciences · 2021Review
- Antinociceptive modulation by the adhesion GPCR CIRL promotes mechanosensory signal discrimination.eLife · 2020Article
- Analyzing chemotherapy-induced peripheral neuropathy in vivo using non-mammalian animal models.Experimental neurology · 2020Review
- Nerve injury drives a heightened state of vigilance and neuropathic sensitization inScience advances · 2019Article
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Axonal degeneration is a molecular self-destruction cascade initiated following traumatic, toxic, and metabolic insults. Its mechanism underlies a number of disorders including hereditary and diabetic neuropathies and the neurotoxic side effects of chemotherapy drugs. Molecules that promote axonal degeneration could represent potential targets for therapy. To identify such molecules, we designed a screening platform based on intoxication of Drosophila larvae with paclitaxel (taxol), a chemotherapeutic agent that causes neuropathy in cancer patients. In Drosophila, taxol treatment causes swelling, fragmentation, and loss of axons in larval peripheral nerves. This axonal loss is not due to apoptosis of neurons. Taxol-induced axonal degeneration in Drosophila shares molecular execution mechanisms with vertebrates, including inhibition by both NMNAT (nicotinamide mononucleotide adenylyltransferase) expression and loss of wallenda/DLK (dual leucine zipper kinase). In a pilot RNAi-based screen we found that knockdown of retinophilin (rtp), which encodes a MORN (membrane occupation and recognition nexus) repeat-containing protein, protects axons from degeneration in the presence of taxol. Loss-of-function mutants of rtp replicate this axonal protection. Knockdown of rtp also delays axonal degeneration in severed olfactory axons. We demonstrate that the mouse ortholog of rtp, MORN4, promotes axonal degeneration in mouse sensory axons following axotomy, illustrating conservation of function. Hence, this new model can identify evolutionarily conserved genes that promote axonal degeneration, and so could identify candidate therapeutic targets for a wide-range of axonopathies.
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