Cdk5 is involved in neuregulin-induced AChR expression at the neuromuscular junction

Here we describe an important involvement of Cdk5/p35 in regulating the gen e expression of acetylcholine receptor (AChR) at the neuromuscular synapse. Cdk5 and p35 were prominently expressed in embryonic muscle, and concentra ted at the neuromuscular junction in adulthood. Neuregulin increased the p3 5-associated Cdk5 kinase activity in the membrane fraction of cultured C2C1 2 myotubes. Co-immunoprecipitation studies revealed the association between Cdk5, p35 and ErbB receptors in muscle and cultured myotubes. Inhibition o f Cdk5 activity not only blocked the NRG-induced AChR transcription, but al so attenuated ErbB activation in cultured myotubes. In light of our finding that overexpression of p35 alone led to an increase in AChR promoter activ ity in muscle, Cdk5 activation is sufficient to mediate the up-regulation o f AChR gene expression. Taken together, these results reveal the unexpected involvement of Cdk5/p35 in neuregulin signaling at the neuromuscular synap se.