Branch-Specific Microtubule Destabilization Mediates Axon Branch Loss during Neuromuscular Synapse Elimination
| العنوان: | Branch-Specific Microtubule Destabilization Mediates Axon Branch Loss during Neuromuscular Synapse Elimination |
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| المؤلفون: | Torben J. Hausrat, Mengzhe Wang, Laura Ruschkies, Tatjana Kleele, Matthias Kneussel, Emily Weigand, Stefan Engelhardt, Matthew Fisher, Miriam S. Reuter, Andrea Ahles, Thomas Misgeld, Natalia A. Marahori, Monika S. Brill, Derron L. Bishop |
| المصدر: | Neuron Neuron 92(4), 845-856 (2016). doi:10.1016/j.neuron.2016.09.049 |
| سنة النشر: | 2016 |
| مصطلحات موضوعية: | 0301 basic medicine, Spastin, metabolism [Cytoskeleton], Spast protein, mouse, metabolism [Microtubules], Neuroscience(all), metabolism [Neuromuscular Junction], Biology, Axonal Transport, Microtubules, Neuromuscular junction, Article, Synapse, 03 medical and health sciences, Mice, Microtubule, medicine, Animals, Telodendron, ddc:610, Axon, Motor Neuron Disease, Microtubule severing, Adenosine Triphosphatases, Mice, Knockout, Neuronal Plasticity, neuromuscular junction, General Neuroscience, cytoskeleton, genetics [Adenosine Triphosphatases], Cell biology, metabolism [Motor Neuron Disease], 030104 developmental biology, medicine.anatomical_structure, nervous system, Axoplasmic transport, metabolism [Adenosine Triphosphatases], synapse elimination, Neuroscience, microtubule |
| الوصف: | Summary Developmental axon remodeling is characterized by the selective removal of branches from axon arbors. The mechanisms that underlie such branch loss are largely unknown. Additionally, how neuronal resources are specifically assigned to the branches of remodeling arbors is not understood. Here we show that axon branch loss at the developing mouse neuromuscular junction is mediated by branch-specific microtubule severing, which results in local disassembly of the microtubule cytoskeleton and loss of axonal transport in branches that will subsequently dismantle. Accordingly, pharmacological microtubule stabilization delays neuromuscular synapse elimination. This branch-specific disassembly of the cytoskeleton appears to be mediated by the microtubule-severing enzyme spastin, which is dysfunctional in some forms of upper motor neuron disease. Our results demonstrate a physiological role for a neurodegeneration-associated modulator of the cytoskeleton, reveal unexpected cell biology of branch-specific axon plasticity and underscore the mechanistic similarities of axon loss in development and disease. Highlights • During synapse elimination, retreating axon branches dismantle their microtubules • Microtubules are destabilized due to branch-specific severing • Microtubule stabilization delays axon branch removal during synapse elimination • The disease-associated microtubule severing protein spastin mediates microtubule loss Brill, Kleele, Ruschkies et al. show that microtubule destabilization mediates dismantling of retreating axon branches and excludes them from organelle delivery by axonal transport. This mechanism is branch specific and involves the neurodegeneration-associated microtubule severing protein spastin. |
| تدمد: | 1097-4199 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::baf965582f3c572f2a15258b4d8c6ed2Test https://pubmed.ncbi.nlm.nih.gov/27773584Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....baf965582f3c572f2a15258b4d8c6ed2 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 10974199 |
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