Academic Journal
The human-specific duplicated α7 gene inhibits the ancestral α7, negatively regulating nicotinic acetylcholine receptor-mediated transmitter release
| العنوان: | The human-specific duplicated α7 gene inhibits the ancestral α7, negatively regulating nicotinic acetylcholine receptor-mediated transmitter release |
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| المؤلفون: | Martín-Sánchez, Carolina, Alés, Eva, Balseiro-Gómez, Santiago, Atienza, Gema, Arnalich Fernández, Francisco, Bordas Sánchez, Anna, Cedillo, José L., Extremera Mazuela, María, Chávez-Reyes, Arturo, Montiel López, Carmen |
| المساهمون: | UAM. Departamento de Farmacología |
| بيانات النشر: | Elsevier |
| سنة النشر: | 2024 |
| المجموعة: | Universidad Autónoma de Madrid (UAM): Biblos-e Archivo |
| مصطلحات موضوعية: | duplicated genes, CHRFAM7A, subunidad dupα7, Medicina |
| الوصف: | Gene duplication generates new functions and traits, enabling evolution. Human-specific duplicated genes in particular are primary sources of innovation during our evolution although they have very few known functions. Here we examine the brain function of one of these genes (CHRFAM7A) and its product (dupα7 subunit). This gene results from a partial duplication of the ancestral CHRNA7 gene encoding the α7 subunit that forms the homopentameric α7 nicotinic acetylcholine receptor (α7-nAChR). The functions of α7-nAChR in the brain are well defined, including the modulation of synaptic transmission and plasticity underlying normal attention, cognition, learning, and memory processes. However, the role of the dupα7 subunit remains unexplored at the neuronal level. Here, we characterize that role by combining immunoblotting, quantitative RT-PCR and FRET techniques with functional assays of α7-nAChR activity using human neuroblastoma SH-SY5Y cell variants with different dupα7 expression levels. Our findings reveal a physical interaction between dupα7 and α7 subunits in fluorescent protein-tagged dupα7/α7 transfected cells that negatively affects normal α7-nAChR activity. Specifically, in both single cells and cell populations, the [Ca2+]i signal and the exocytotic response induced by selective stimulation of α7-nAChR were either significantly inhibited by stable dupα7 overexpression or augmented after silencing dupα7 gene expression with specific siRNAs. These findings identify a new role for the dupα7 subunit as a negative regulator of α7-nAChR-mediated control of exocytotic neurotransmitter release. If this effect is excessive, it would result in an impaired synaptic transmission that could underlie the neurocognitive and neuropsychiatric disorders associated with α7-nAChR dysfunction ; This work was supported by a Grant from the Ministry of Economy, Industry and Competitiveness, Government of Spain (SAF2017-82689-R) to C. M. and F. A. C. M. -S. was recipient of an FPI fellowship (Ministry of Economy, Industry and ... |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| Relation: | Journal of Biological Chemistry; https://doi.org/10.1016/j.jbc.2021.100341; Gobierno de España. SAF2017-82689-R; Journal of biological chemistry 296 (2021): 100341; http://hdl.handle.net/10486/715398; 296 |
| DOI: | 10.1016/J.JBC.2021.100341 |
| الاتاحة: | http://hdl.handle.net/10486/715398 https://doi.org/10.1016/J.JBC.2021.100341 |
| Rights: | © 2021 the authors ; http://creativecommons.org/licenses/by/4.0/ ; Reconocimiento ; openAccess |
| رقم الانضمام: | edsbas.CB9DBBE9 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1016/J.JBC.2021.100341 |
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