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dc.contributor.author
Huang, Yung Chi
dc.contributor.author
Pirri, Jennifer K.
dc.contributor.author
Rayes, Diego Hernán
dc.contributor.author
Gao, Shangbang
dc.contributor.author
Mulcahy, Ben
dc.contributor.author
Grant, Jeff
dc.contributor.author
Saheki, Yasunori
dc.contributor.author
Francis, Michael M.
dc.contributor.author
Zhen, Mei
dc.contributor.author
Alkema, Mark J.
dc.date.available
2020-03-10T17:56:30Z
dc.date.issued
2019-08-05
dc.identifier.citation
Huang, Yung Chi; Pirri, Jennifer K.; Rayes, Diego Hernán; Gao, Shangbang; Mulcahy, Ben; et al.; Gain-of-function mutations in the UNC-2/CaV2α channel lead to excitation-dominant synaptic transmission in C. elegans; eLife Sciences Publications Ltd; eLife; 8; 05-8-2019; 1-28
dc.identifier.issn
2050-084X
dc.identifier.uri
http://hdl.handle.net/11336/99040
dc.description.abstract
Mutations in pre-synaptic voltage gated calcium channels can lead to familial hemiplegic migraine type 1 (FHM1). While mammalian studies indicate that the migraine brain is hyperexcitable due to enhanced excitation or reduced inhibition, the molecular and cellular mechanisms underlying this excitatory/inhibitory (E/I) imbalance are poorly understood. We identified a gain-of-function (gf) mutation in the Caenorhabditis elegans CaV2 channel α1 subunit, UNC-2, which leads to increased calcium currents. unc-2(zf35gf) mutants exhibit hyperactivity and seizure-like motor behaviors. Expression of the unc-2 gene with FHM1 substitutions R192Q and S218L leads to hyperactivity similar to that of unc-2(zf35gf) mutants. unc-2(zf35gf) mutants display increased cholinergic-and decreased GABAergic-transmission. Moreover, increased cholinergic transmission in unc-2(zf35gf) mutants leads to an increase of cholinergic synapses and a TAX-6/calcineurin dependent reduction of GABA synapses. Our studies reveal mechanisms through which CaV2 gain-of-function mutations disrupt excitation-inhibition balance in the nervous system.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
eLife Sciences Publications Ltd
dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by/2.5/ar/
dc.subject
CaV2
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C. elegans
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Hyperactivity
dc.subject
Gain of function
dc.subject.classification
Bioquímica y Biología Molecular
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Ciencias Biológicas
dc.subject.classification
CIENCIAS NATURALES Y EXACTAS
dc.title
Gain-of-function mutations in the UNC-2/CaV2α channel lead to excitation-dominant synaptic transmission in C. elegans
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2020-02-26T20:09:16Z
dc.journal.volume
8
dc.journal.pagination
1-28
dc.journal.pais
Reino Unido
dc.journal.ciudad
Cambridge
dc.description.fil
Fil: Huang, Yung Chi. University of Massachussets; Estados Unidos
dc.description.fil
Fil: Pirri, Jennifer K.. University of Massachussets; Estados Unidos
dc.description.fil
Fil: Rayes, Diego Hernán. University of Massachussets; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina
dc.description.fil
Fil: Gao, Shangbang. Mount Sinai Hospital; Estados Unidos
dc.description.fil
Fil: Mulcahy, Ben. Mount Sinai Hospital; Estados Unidos
dc.description.fil
Fil: Grant, Jeff. University of Massachussets; Estados Unidos
dc.description.fil
Fil: Saheki, Yasunori. The Rockefeller University; Estados Unidos
dc.description.fil
Fil: Francis, Michael M.. University of Massachussets; Estados Unidos
dc.description.fil
Fil: Zhen, Mei. University of Toronto; Canadá. Mount Sinai Hospital; Estados Unidos
dc.description.fil
Fil: Alkema, Mark J.. University of Massachussets; Estados Unidos
dc.journal.title
eLife
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://elifesciences.org/articles/45905
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.7554/eLife.45905
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