Nestin negatively regulates postsynaptic differentiation of the neuromuscular synapse

Yang, Dominguez, de Winter, Gould, John Eriksson, Lee

    Tutkimustuotos: LehtiartikkeliArtikkeliTieteellinenvertaisarvioitu

    36 Sitaatiot (Scopus)

    Abstrakti

    Positive and negative regulation of neurotransmitter receptor aggregation on the postsynaptic membrane is a critical event during synapse formation. Acetylcholine (ACh) and agrin are two opposing signals that regulate ACh receptor (AChR) clustering during neuromuscular junction (NMJ) development. ACh induces dispersion of AChR clusters that are not stabilized by agrin via a cyclin-dependent kinase 5 (Cdk5)-mediated mechanism, but regulation of Cdk5 activation is poorly understood. We found that the intermediate filament protein nestin physically interacts with Cdk5 and is required for ACh-induced association of p35, the co-activator of Cdk5, with the muscle membrane. Blockade of nestin-dependent signaling inhibited ACh-induced Cdk5 activation and the dispersion of AChR clusters in cultured myotubes. Similar to the effects of Cdk5 gene inactivation, knockdown of nestin in agrin-deficient mouse embryos substantially restored AChR clusters. These results suggest that nestin is required for ACh-induced, Cdk5-dependent dispersion of AChR clusters during NMJ development.
    AlkuperäiskieliEi tiedossa
    Sivut324–330
    JulkaisuNature Neuroscience
    Vuosikerta14
    Numero3
    DOI - pysyväislinkit
    TilaJulkaistu - 2011
    OKM-julkaisutyyppiA1 Julkaistu artikkeli, soviteltu

    Viittausmuodot