Drosophila Nesprin-1 controls glutamate receptor density at neuromuscular junctions.
Cell Mol Life Sci
; 71(17): 3363-79, 2014 Sep.
Article
em En
| MEDLINE
| ID: mdl-24492984
Nesprin-1 is a core component of a protein complex connecting nuclei to cytoskeleton termed LINC (linker of nucleoskeleton and cytoskeleton). Nesprin-1 is anchored to the nuclear envelope by its C-terminal KASH domain, the disruption of which has been associated with neuronal and neuromuscular pathologies, including autosomal recessive cerebellar ataxia and Emery-Dreifuss muscular dystrophy. Here, we describe a new and unexpected role of Drosophila Nesprin-1, Msp-300, in neuromuscular junction. We show that larvae carrying a deletion of Msp-300 KASH domain (Msp-300 (∆KASH) ) present a locomotion defect suggestive of a myasthenia, and demonstrate the importance of muscle Msp-300 for this phenotype, using tissue-specific RNAi knock-down. We show that Msp-300 (∆KASH) mutants display abnormal neurotransmission at the larval neuromuscular junction, as well as an imbalance in postsynaptic glutamate receptor composition with a decreased percentage of GluRIIA-containing receptors. We could rescue Msp-300 (∆KASH) locomotion phenotypes by GluRIIA overexpression, suggesting that the locomotion impairment associated with the KASH domain deletion is due to a reduction in junctional GluRIIA. In summary, we found that Msp-300 controls GluRIIA density at the neuromuscular junction. Our results suggest that Drosophila is a valuable model for further deciphering how Nesprin-1 and LINC disruption may lead to neuronal and neuromuscular pathologies.
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Base de dados:
MEDLINE
Assunto principal:
Receptores de Glutamato
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Proteínas de Drosophila
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Drosophila melanogaster
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Proteínas dos Microfilamentos
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Proteínas Musculares
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Junção Neuromuscular
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article