Best1 is a gene regulated by nerve injury and required for Ca 2+-activated Cl- current expression in axotomized sensory neurons

Mathieu Boudes, Chamroeun Sar, Aurélie Menigoz, Cécile Hilaire, Marie O. Péquignot, Alexei Kozlenkov, Alan D Marmorstein, Patrick Carroll, Jean Valmier, Frédérique Scamps

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)10063-10071
Number of pages9
JournalJournal of Neuroscience
Volume29
Issue number32
DOIs
StatePublished - Aug 12 2009
Externally publishedYes

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Sensory Receptor Cells
Chlorides
Wounds and Injuries
Genes
Neurons
Spinal Ganglia
RNA Interference
Green Fluorescent Proteins
In Situ Hybridization
Blood Proteins
Membrane Proteins
Up-Regulation
Cell Membrane
Pharmacology
Proteins

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Best1 is a gene regulated by nerve injury and required for Ca 2+-activated Cl- current expression in axotomized sensory neurons. / Boudes, Mathieu; Sar, Chamroeun; Menigoz, Aurélie; Hilaire, Cécile; Péquignot, Marie O.; Kozlenkov, Alexei; Marmorstein, Alan D; Carroll, Patrick; Valmier, Jean; Scamps, Frédérique.

In: Journal of Neuroscience, Vol. 29, No. 32, 12.08.2009, p. 10063-10071.

Research output: Contribution to journalArticle

Boudes, M, Sar, C, Menigoz, A, Hilaire, C, Péquignot, MO, Kozlenkov, A, Marmorstein, AD, Carroll, P, Valmier, J & Scamps, F 2009, 'Best1 is a gene regulated by nerve injury and required for Ca 2+-activated Cl- current expression in axotomized sensory neurons', Journal of Neuroscience, vol. 29, no. 32, pp. 10063-10071. https://doi.org/10.1523/JNEUROSCI.1312-09.2009
Boudes, Mathieu ; Sar, Chamroeun ; Menigoz, Aurélie ; Hilaire, Cécile ; Péquignot, Marie O. ; Kozlenkov, Alexei ; Marmorstein, Alan D ; Carroll, Patrick ; Valmier, Jean ; Scamps, Frédérique. / Best1 is a gene regulated by nerve injury and required for Ca 2+-activated Cl- current expression in axotomized sensory neurons. In: Journal of Neuroscience. 2009 ; Vol. 29, No. 32. pp. 10063-10071.
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