The human-specific duplicated α7 gene inhibits the ancestral α7, negatively regulating nicotinic acetylcholine receptor-mediated transmitter release

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dc.contributor.advisorCarmen Montieles
dc.contributor.advisorArturo Chavez-Reyeses
dc.contributor.authorMartín-Sánchez, Carolinaes
dc.contributor.authorAlés, Evaes
dc.contributor.authorBalseiro-Gómez, Santiagoes
dc.contributor.authorAtienza, Gemaes
dc.contributor.authorArnalich, Franciscoes
dc.contributor.authorBordas, Annaes
dc.contributor.authorCedillo, José Les
dc.contributor.authorExtremera, Maríaes
dc.contributor.authorChávez-Reyes, Arturoes
dc.contributor.authorMontiel, Carmenes
dc.date.accessioned2023-05-18T15:12:25Z
dc.date.available2023-05-18T15:12:25Z
dc.date.issued2020-10-22
dc.description.abstractGene duplication generates new functions and traits, enabling evolution. Human-specific duplicated genes in particular are primary sources of innovation during our evo- lution 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 modula- tion of synaptic transmission and plasticity underlying normal attention, cognition, learning, and memory processes. Howev- er, 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 exces- sive, it would result in an impaired synaptic transmission that could underlie the neurocognitive and neuropsychiatric dis- orders associated with α7-nAChR dysfunction.en_US
dc.identifier.citationJournal of Biological Chemistry, Vol. 296, N° January-June (2021)en_US
dc.identifier.issn0021-9258en_US
dc.identifier.orcid0000-0002-6655-815Xes
dc.identifier.orcid0000-0003-4845-0484es
dc.identifier.orcidhttps://doi.org/10.1016/j.jbc.2021.100341
dc.identifier.urihttp://hdl.handle.net/20.500.12254/3254
dc.language.isoenen_US
dc.publisherAmerican Society for Biochemistry and Molecular Biologyen_US
dc.rightsAtribución-NoComercial-CompartirIgual 3.0 Chile (CC BY-NC-SA 3.0 CL)
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/3.0/cl/
dc.subject.otherDupa7en_US
dc.subject.othera7-nAChRen_US
dc.subject.otherAncestral α7en_US
dc.subject.otherNicotinic acetylcholine receptoren_US
dc.subject.otherCHRFAM7Aen_US
dc.subject.otherDupα7 subuniten_US
dc.titleThe human-specific duplicated α7 gene inhibits the ancestral α7, negatively regulating nicotinic acetylcholine receptor-mediated transmitter releaseen_US
dc.typeArtículoes
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