Spinal Motoneuron TMEM16F Acts at C-boutons to Modulate Motor Resistance and Contributes to ALS Pathogenesis.
Cell Rep
; 30(8): 2581-2593.e7, 2020 02 25.
Article
en En
| MEDLINE
| ID: mdl-32101737
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 (CaCCs) remain unclear. Here, we demonstrate that TMEM16F governs a Ca2+-activated Cl- conductance in spinal motoneurons. We show that TMEM16F is expressed in synaptic clusters facing pre-synaptic cholinergic C-boutons in α-motoneurons of the spinal cord. Mice with targeted exon deletion in Tmem16f display decreased motor performance under high-demanding tasks attributable to an increase in the recruitment threshold of fast α-motoneurons. Remarkably, loss of TMEM16F function in a mouse model of amyotrophic lateral sclerosis (ALS) significantly reduces expression of an activity-dependent early stress marker and muscle denervation, delays disease onset, and preserves muscular strength only in male ALS mice. Thus, TMEM16F controls motoneuron excitability and impacts motor resistance as well as motor deterioration in ALS.
Palabras clave
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Médula Espinal
/
Terminales Presinápticos
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Proteínas de Transferencia de Fosfolípidos
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Anoctaminas
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Esclerosis Amiotrófica Lateral
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Actividad Motora
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Neuronas Motoras
Tipo de estudio:
Etiology_studies
Idioma:
En
Revista:
Cell Rep
Año:
2020
Tipo del documento:
Article