Formin Activity and mDia1 Contribute to Maintain Axon Initial Segment Composition and Structure
| العنوان: | Formin Activity and mDia1 Contribute to Maintain Axon Initial Segment Composition and Structure |
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| المؤلفون: | Juan José Garrido, Pablo Mendez, Michaël Russier, Diana Retana, Norah Boumedine-Guignon, Wei Zhang, Beatriz Achón, Dominique Debanne, Maria Ciorraga |
| المساهمون: | Unité de Neurobiologie des canaux Ioniques et de la Synapse (UNIS - Inserm U1072), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Ministerio de Ciencia, Innovación y Universidades (España), Conferencia de Rectores de las Universidades Españolas, China Scholarship Council, Universidad Autónoma de Madrid |
| المصدر: | Molecular Neurobiology Molecular Neurobiology, 2021, ⟨10.1007/s12035-021-02531-6⟩ Digital.CSIC. Repositorio Institucional del CSIC instname Molecular Neurobiology, Humana Press, 2021, ⟨10.1007/s12035-021-02531-6⟩ |
| بيانات النشر: | Springer Science and Business Media LLC, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Neuroscience (miscellaneous), Formins, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, macromolecular substances, Hippocampus, Microtubules, Article, Mice, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, AnkyrinG, Microtubule, mDia1, medicine, Animals, Axon, Cytoskeleton, Cells, Cultured, Actin, 030304 developmental biology, Neurons, 0303 health sciences, biology, Chemistry, Sodium channel, Axon initial segment, Axons, Cell biology, medicine.anatomical_structure, Neurology, biology.protein, MDia1, 030217 neurology & neurosurgery |
| الوصف: | The axon initial segment (AIS) is essential for maintaining neuronal polarity, modulating protein transport into the axon, and action potential generation. These functions are supported by a distinctive actin and microtubule cytoskeleton that controls axonal trafficking and maintains a high density of voltage-gated ion channels linked by scaffold proteins to the AIS cytoskeleton. However, our knowledge of the mechanisms and proteins involved in AIS cytoskeleton regulation to maintain or modulate AIS structure is limited. In this context, formins play a significant role in the modulation of actin and microtubules. We show that pharmacological inhibition of formins modifies AIS actin and microtubule characteristics in cultured hippocampal neurons, reducing F-actin density and decreasing microtubule acetylation. Moreover, formin inhibition diminishes sodium channels, ankyrinG and ßIV-spectrin AIS density, and AIS length, in cultured neurons and brain slices, accompanied by decreased neuronal excitability. We show that genetic downregulation of the mDia1 formin by interference RNAs also decreases AIS protein density and shortens AIS length. The ankyrinG decrease and AIS shortening observed in pharmacologically inhibited neurons and neuron-expressing mDia1 shRNAs were impaired by HDAC6 downregulation or EB1-GFP expression, known to increase microtubule acetylation or stability. However, actin stabilization only partially prevented AIS shortening without affecting AIS protein density loss. These results suggest that mDia1 maintain AIS composition and length contributing to the stability of AIS microtubules. Open Access funding provided thanks to the CRUE-CSIC agreement with Springer Nature. The work was supported by agrant from Ministerio de Ciencia y Universidades (RTI2018-095156-B-100) to JJG and INSERM funding to DD. Wei Zhang was supported by a fellowship from China Scholarship Council (No.201506300085) and Beatriz Achon by a Master fellowship from Universidad Autónoma de Madrid. |
| تدمد: | 1559-1182 0893-7648 |
| DOI: | 10.1007/s12035-021-02531-6 |
| DOI: | 10.1007/s12035-021-02531-6⟩ |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d48fd22dac612831af9667dacc1b1546 https://doi.org/10.1007/s12035-021-02531-6 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....d48fd22dac612831af9667dacc1b1546 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15591182 08937648 |
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| DOI: | 10.1007/s12035-021-02531-6 |