Artículo
Gain-of-function mutations in the UNC-2/CaV2α channel lead to excitation-dominant synaptic transmission in C. elegans
Huang, Yung Chi; Pirri, Jennifer K.; Rayes, Diego Hernán
; Gao, Shangbang; Mulcahy, Ben; Grant, Jeff; Saheki, Yasunori; Francis, Michael M.; Zhen, Mei; Alkema, Mark J.
Fecha de publicación:
05/08/2019
Editorial:
eLife Sciences Publications Ltd
Revista:
eLife
ISSN:
2050-084X
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
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.
Palabras clave:
CaV2
,
C. elegans
,
Hyperactivity
,
Gain of function
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Articulos(INIBIBB)
Articulos de INST.DE INVEST.BIOQUIMICAS BAHIA BLANCA (I)
Articulos de INST.DE INVEST.BIOQUIMICAS BAHIA BLANCA (I)
Citación
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
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