ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2005
Axonal dynactin p150Glued transports caspase-8 to drive retrograde olfactory receptor neuron apoptosis.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 51 citations in OpenAlex.
- Caspases in the Developing Central Nervous System: Apoptosis and Beyond.Frontiers in cell and developmental biology · 2021Review
- Role of Caspase-8 and Fas in Cell Death After Spinal Cord Injury.Frontiers in molecular neuroscience · 2018Review
- Retrograde apoptotic signaling by the p75 neurotrophin receptor.Neuronal signaling · 2017Review
- Retrograde Activation of the Extrinsic Apoptotic Pathway in Spinal-Projecting Neurons after a Complete Spinal Cord Injury in Lampreys.BioMed research international · 2017Article
- Local caspase activation interacts with Slit-Robo signaling to restrict axonal arborization.The Journal of cell biology · 2013Article
- Critical role of GFRα1 in the development and function of the main olfactory system.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2012Article
- Leucine-rich repeat kinase 2 for beginners: six key questions.Cold Spring Harbor perspectives in medicine · 2012Review
- LRRK2 Parkinson disease mutations enhance its microtubule association.Human molecular genetics · 2012Article
- Use of fluorochrome-labeled inhibitors of caspases to detect neuronal apoptosis in the whole-mounted lamprey brain after spinal cord injury.Enzyme research · 2012Article
- In vivo olfactory model of APP-induced neurodegeneration reveals a reversible cell-autonomous function.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2011Article
- Fas-associated factor 1 as a regulator of olfactory axon guidance.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2011Article
- Uncx regulates proliferation of neural progenitor cells and neuronal survival in the olfactory epithelium.Molecular and cellular neurosciences · 2010Article
- State-dependent sculpting of olfactory sensory neurons is attributed to sensory enrichment, odor deprivation, and aging.Neuroscience letters · 2010Article
- Retrograde axonal transport: pathways to cell death?Trends in neurosciences · 2010Review
- Chemical stress induces the unfolded protein response in olfactory sensory neurons.The Journal of comparative neurology · 2010Article
- Axotomy-induced neurotrophic withdrawal causes the loss of phenotypic differentiation and downregulation of NGF signalling, but not death of septal cholinergic neurons.Molecular neurodegeneration · 2010Article
- Sequential onset of presynaptic molecules during olfactory sensory neuron maturation.The Journal of comparative neurology · 2009Article
- Long-term survival of olfactory sensory neurons after target depletion.The Journal of comparative neurology · 2009Article
- A switch in retrograde signaling from survival to stress in rapid-onset neurodegeneration.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2009Article
- Semaphorin 5B mediates synapse elimination in hippocampal neurons.Neural development · 2009Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Olfactory receptor neurons (ORNs) undergo caspase-mediated retrograde apoptosis after target removal (bulbectomy), in which axonal caspase-9 and caspase-3 activation leads to terminal apoptosis in ORN soma of the olfactory epithelium. Here, we show that caspase-8 can act as an initiator of ORN apoptosis after bulbectomy and also after synaptic instability is induced by NMDA-mediated excitotoxic death of ORN target neurons in the olfactory bulb. Caspase-8 and caspase-3 are sequentially activated within ORN presynaptic terminals, and caspase-8 complexes with dynactin p150Glued, (a retrograde motor protein) and is transported retrogradely, preceding axonal caspase-3 activation and apoptosis of ORN cell bodies. Focal in vivo inhibition of initiator caspase activation or microtubule-dependent transport (with Taxol) at the lesioned axon terminus results in a significant reduction in retrograde axonal caspase-8 and caspase-3 activation and inhibition of retrograde ORN death. Caspase-8 activation and retrograde transport after NMDA lesion is similarly reduced in mice null for p75, the low-affinity nerve growth factor receptor. The retrograde apoptosis of ORNs thus involves a novel mechanism that used p75 in the local activation of caspase-8. Once caspase-8 is maximally activated in the presynaptic terminal, it is transported retrogradely by the motor complex dynactin/dynein, a process that can be inhibited focally to inhibit ORN apoptosis after acute axonal lesion. These data have revealed a novel mechanism of retrograde apoptosis, in which caspase-8 complexes directly with axonal dynactin p150Glued to reveal a differential vulnerability of subpopulations of ORNs to undergo apoptosis after axonal damage and the loss of olfactory bulb target neurons.
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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.