Developmental defects in Huntington’s disease show that axonal growth and microtubule reorganization require NUMA1
| Autor: | Mariacristina Capizzi, Rémi Carpentier, Yohann Couté, Rayane Kassem, Eric Denarier, Annie Adrait, Marina Mapelli, Sandrine Humbert |
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| Přispěvatelé: | [GIN] Grenoble Institut des Neurosciences (GIN), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), Etude de la dynamique des protéomes (EDyP), BioSanté (UMR BioSanté), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA), ANR-17-EURE-0003,CBH-EUR-GS,CBH-EUR-GS(2017), ANR-18-CE16-0009,AXYON,Transport axonal et maturation neuronale: conséquences pour la fonction synaptique et les connexions neuronales en situation normale et dans la maladie de Huntington.(2018) |
| Rok vydání: | 2022 |
| Předmět: |
Proteomics
[SDV]Life Sciences [q-bio] Growth Cones Cell Cycle Proteins Biology Corpus callosum Microtubules Axonal growth cone axonal growth Mice Huntington's disease Microtubule medicine microtubule bundling Animals Progenitor cell Cytoskeleton Growth cone neurodevelopment General Neuroscience nuclear/mitotic apparatus protein 1 (NUMA1) medicine.disease Axons Cell biology Huntington Disease Intracellular Huntington’s disease |
| Zdroj: | Neuron Neuron, 2022, 110 (1), pp.36-50.e5. ⟨10.1016/j.neuron.2021.10.033⟩ |
| ISSN: | 0896-6273 |
| Popis: | Summary Although the classic symptoms of Huntington’s disease (HD) manifest in adulthood, neural progenitor cell behavior is already abnormal by 13 weeks’ gestation. To determine how these developmental defects evolve, we turned to cell and mouse models. We found that layer II/III neurons that normally connect the hemispheres are limited in their growth in HD by microtubule bundling defects within the axonal growth cone, so that fewer axons cross the corpus callosum. Proteomic analyses of the growth cones revealed that NUMA1 (nuclear/mitotic apparatus protein 1) is downregulated in HD by miR-124. Suppressing NUMA1 in wild-type cells recapitulates the microtubule and axonal growth defects of HD, whereas raising NUMA1 levels with antagomiR-124 or stabilizing microtubules with epothilone B restores microtubule organization and rescues axonal growth. NUMA1 therefore regulates the microtubule network in the growth cone, and HD, which is traditionally conceived as a disease of intracellular trafficking, also disturbs the cytoskeletal network. |
| Databáze: | OpenAIRE |
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