Synergistic effects of neuregulin and agrin on muscle acetylcholine receptor expression.
Mol Cell Neurosci
; 26(4): 558-69, 2004 Aug.
Article
em En
| MEDLINE
| ID: mdl-15276157
ABSTRACT
The proper function of neuromuscular junctions requires an extremely high density of acetylcholine receptors (AChRs) that may be achieved from neuron-derived factors including agrin and neuregulin. Here, we show that neuregulin-1 and agrin co-localize at neuromuscular junctions in vivo and form complexes when co-transfected into COS-7 cells. When these COS-7 cells are cultured with myotubes, synergistic effects are observed for AChR clustering, membrane insertion of new AChRs, and induction of AChR mRNA. Even a muscle form of agrin that lacks intrinsic clustering activities by itself, significantly enhances neuregulin-induced clustering and insertion of AChRs. While the heparin-binding (A) domain of agrin is required for agrin localization in the extracellular matrix adjacent to AChR clusters, the heparan sulfate-containing domain of agrin is needed for the synergistic effects and co-localization with neuregulin-1. These results suggest that matrix interactions between exogenously supplied agrin and neuregulin-1 on the muscle surface provide a localized source of signaling factors needed to produce high densities of AChRs at neuromuscular junctions.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Receptores Nicotínicos
/
Agrina
/
Músculo Esquelético
/
Fibras Musculares Esqueléticas
/
Proteínas Aviárias
/
Proteínas do Tecido Nervoso
/
Junção Neuromuscular
Idioma:
En
Revista:
Mol Cell Neurosci
Assunto da revista:
BIOLOGIA MOLECULAR
/
NEUROLOGIA
Ano de publicação:
2004
Tipo de documento:
Article
País de afiliação:
Estados Unidos