Best1 Is a Gene Regulated by Nerve Injury and Required for Ca2+-Activated Cl- Current Expression in Axotomized Sensory Neurons

被引：39

作者：

Boudes, Mathieu ^{[1
,2
]}

Sar, Chamroeun ^{[1
]}

Menigoz, Aurelie ^{[1
,2
]}

Hilaire, Cecile ^{[1
]}

Pequignot, Marie O. ^{[1
]}

Kozlenkov, Alexei ^{[1
]}

Marmorstein, Alan ^{[3
]}

Carroll, Patrick ^{[1
]}

Valmier, Jean ^{[1
,2
]}

Scamps, Frederique ^{[1
]}

机构：

[1] INSERM, U583, F-34000 Montpellier, France

[2] Univ Montpellier 2, F-34000 Montpellier, France

[3] Univ Arizona, Dept Ophthalmol & Vis Sci, Tucson, AZ 85724 USA

来源：

JOURNAL OF NEUROSCIENCE | 2009年 / 29卷 / 32期

基金：

美国国家卫生研究院;

关键词：

VITELLIFORM MACULAR DYSTROPHY; CALCIUM-ACTIVATED CURRENTS; RETINAL-PIGMENT EPITHELIUM; DORSAL-ROOT GANGLION; SCIATIC-NERVE; CHLORIDE CHANNELS; CA2+ CHANNELS; PROTEIN; FAMILY; REGENERATION;

D O I：

10.1523/JNEUROSCI.1312-09.2009

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

We investigated the molecular determinants of Ca2+-activated chloride current (CaCC) expressed in adult sensory neurons after a nerve injury. Dorsal root ganglia express the transcripts of three gene families known to induce CaCCs in heterologous systems: bestrophin, tweety, and TMEM16. We found with quantitative transcriptional analysis and in situ hybridization that nerve injury induced upregulation of solely bestrophin-1 transcripts in sensory neurons. Gene screening with RNA interference in single neurons demonstrated that mouse Best1 is required for the expression of CaCC in injured sensory neurons. Transfecting injured sensory neurons with bestrophin-1 mutants inhibited endogenous CaCC. Exogenous expression of the fusion protein green fluorescent protein-Bestrophin-1 in naive neurons demonstrated a plasma membrane localization of the protein that generates a CaCC with biophysical and pharmacological properties similar to endogenous CaCC. Our data suggest that Best1 belongs to a group of genes upregulated by nerve injury and supports functional CaCC expression in injured sensory neurons.

引用

页码：10063 / 10071

页数：9

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