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The Calcium-Activated Chloride Channel TMEM16F Acts at C-Bouton to Modulate Motor Resistance and Contributes to ALS Pathogenesis

32 Pages Posted: 23 Jul 2019 Publication Status: Published

See all articles by Claire Soulard

Claire Soulard

University of Montpellier - The Neuroscience Institute of Montpellier

Céline Salsac

University of Montpellier - The Neuroscience Institute of Montpellier

Kevin Mouzat

UNIMES - Université de Nîmes - Department of Biochemistry

Cécile Hilaire

University of Montpellier - The Neuroscience Institute of Montpellier

Julien Roussel

University of Montpellier - The Neuroscience Institute of Montpellier

Alexandre Mezghrani

University of Montpellier - The Neuroscience Institute of Montpellier

Serge Lumbroso

UNIMES - Université de Nîmes - Department of Biochemistry

Cédric Raoul

University of Montpellier - The Neuroscience Institute of Montpellier

Frederique Scamps

University of Montpellier - The Neuroscience Institute of Montpellier

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Abstract

Neuronal Ca2+ entry elicited by electrical activity contributes to information coding via activation of K+ and Cl- channels. While Ca2+-dependent K+ channels have been extensively studied, the molecular identity and role of Ca2+-activated Cl- channels (CaCC) remains however unclear. Here, we show the CaCC encoded by Tmem16f is specifically expressed as clusters in α-motoneurons of the ventral spinal cord facing the pre-synaptic cholinergic C-boutons. Tmem16f-deficient mice display decreased motor performance under high-task exercise attributable to an increase of recruitment threshold of fast α-motoneurons. Remarkably, the deletion of TMEM16F in a mouse model of the amyotrophic lateral sclerosis (ALS) significantly reduces activity-dependent early stress marker expression, muscle denervation, preserves muscular force and delays disease progression. Thus, as a novel component of C-bouton, TMEM16F controls motoneuron excitability and impacts motor resistance as well as motor deterioration in ALS.

Keywords: C-bouton, muscarinic regulation, electrical activity, spinal motoneuron, Anoctamine 6, amyotrophic lateral sclerosis

Suggested Citation

Soulard, Claire and Salsac, Céline and Mouzat, Kevin and Hilaire, Cécile and Roussel, Julien and Mezghrani, Alexandre and Lumbroso, Serge and Raoul, Cédric and Scamps, Frederique, The Calcium-Activated Chloride Channel TMEM16F Acts at C-Bouton to Modulate Motor Resistance and Contributes to ALS Pathogenesis (July 22, 2019). Available at SSRN: https://ssrn.com/abstract=3424314 or http://dx.doi.org/10.2139/ssrn.3424314
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Claire Soulard

University of Montpellier - The Neuroscience Institute of Montpellier

France

Céline Salsac

University of Montpellier - The Neuroscience Institute of Montpellier

France

Kevin Mouzat

UNIMES - Université de Nîmes - Department of Biochemistry

Place du Pr R. Debré
CEDEX 9
Nîmes, 30029
France

Cécile Hilaire

University of Montpellier - The Neuroscience Institute of Montpellier

France

Julien Roussel

University of Montpellier - The Neuroscience Institute of Montpellier

France

Alexandre Mezghrani

University of Montpellier - The Neuroscience Institute of Montpellier

France

Serge Lumbroso

UNIMES - Université de Nîmes - Department of Biochemistry

Place du Pr R. Debré
CEDEX 9
Nîmes, 30029
France

Cédric Raoul

University of Montpellier - The Neuroscience Institute of Montpellier

France

Frederique Scamps (Contact Author)

University of Montpellier - The Neuroscience Institute of Montpellier ( email )

France

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