Nestin negatively regulates postsynaptic differentiation of the neuromuscular synapse

A1 Originalartikel i en vetenskaplig tidskrift (referentgranskad)

Interna författare/redaktörer

Publikationens författare: Yang, Dominguez, de Winter, Gould, Eriksson, Lee
Publiceringsår: 2011
Tidskrift: Nature Neuroscience
Tidskriftsakronym: Nat Neurosci
Volym: 14
Nummer: 3
Artikelns första sida, sidnummer: 324
Artikelns sista sida, sidnummer: 330
ISSN: 1546-1726


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.

Senast uppdaterad 2020-02-04 vid 02:26