دورية أكاديمية
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: | Zhang, Wei, Ciorraga, Maria, Méndez, Pablo, Retana, Diana, Boumedine-Guignon, Norah, Achón Buil, Beatriz, Russier, Michael, Debanne, Dominique, Garrido Jurado, Juan José |
| المساهمون: | Ministerio de Ciencia, Innovación y Universidades (España), Conferencia de Rectores de las Universidades Españolas, China Scholarship Council, Universidad Autónoma de Madrid |
| بيانات النشر: | Humana Press |
| سنة النشر: | 2021 |
| المجموعة: | Digital.CSIC (Consejo Superior de Investigaciones Científicas / Spanish National Research Council) |
| مصطلحات موضوعية: | AnkyrinG, Axon initial segment, Formins, Microtubules, mDia1 |
| 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. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | unknown |
| تدمد: | 0893-7648 |
| العلاقة: | #PLACEHOLDER_PARENT_METADATA_VALUE#; info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/RTI2018-095156-B-I00/ES/PLASTICIDAD E INTEGRIDAD DEL SEGMENTO INICIAL DEL AXON: MECANISMOS REGULATORIOS, IMPLICACION EN ENFERMEDADES DEL SISTEMA NERVIOSO Y PREVENCION/; Publisher's version; http://dx.doi.org/10.1007/s12035-021-02531-6Test; Sí; Molecular Neurobiology 58: 6153- 6169 (2021); http://hdl.handle.net/10261/260415Test; http://dx.doi.org/10.13039/501100004543Test; http://dx.doi.org/10.13039/501100004593Test |
| DOI: | 10.1007/s12035-021-02531-6 |
| DOI: | 10.13039/501100004543 |
| DOI: | 10.13039/501100004593 |
| الإتاحة: | https://doi.org/10.1007/s12035-021-02531-6Test https://doi.org/10.13039/501100004543Test https://doi.org/10.13039/501100004593Test http://hdl.handle.net/10261/260415Test |
| حقوق: | open |
| رقم الانضمام: | edsbas.7F888567 |
| قاعدة البيانات: | BASE |
| تدمد: | 08937648 |
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| DOI: | 10.1007/s12035-021-02531-6 |