Cdk5 is involved in neuregulin-induced AChR expression at the neuromuscular junction.
Here we describe an important involvement of Cdk5/p35 in regulating the gene expression of acetylcholine receptor (AChR) at the neuromuscular synapse. Cdk5 and p35 were prominently expressed in embryonic muscle, and concentrated at the neuromuscular junction in adulthood. Neuregulin increased the p35-associated Cdk5 kinase activity in the membrane fraction of cultured C2C12 myotubes. Co-immunoprecipitation studies revealed the association between Cdk5, p35 and ErbB receptors in muscle and cultured myotubes. Inhibition of Cdk5 activity not only blocked the NRG-induced AChR transcription, but also attenuated ErbB activation in cultured myotubes. In light of our finding that overexpression of p35 alone led to an increase in AChR promoter activity in muscle, Cdk5 activation is sufficient to mediate the up-regulation of AChR gene expression. Taken together, these results reveal the unexpected involvement of Cdk5/p35 in neuregulin signaling at the neuromuscular synapse.
Fu
A K
AK
Department of Biochemistry, Biotechnology Research Institute, Molecular Neuroscience Center, Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, China.
Fu
W Y
WY
Cheung
J
J
Tsim
K W
KW
Ip
F C
FC
Wang
J H
JH
Ip
N Y
NY
D000818:Animals; D015153:Blotting, Western; D001923:Brain Chemistry; D002458:Cell Fractionation; D002460:Cell Line; D002642:Chick Embryo; D051360:Cyclin-Dependent Kinase 5; D018844:Cyclin-Dependent Kinases / Q000378:metabolism*; D004622:Embryo, Mammalian / Q000502:physiology; D005786:Gene Expression Regulation; D007150:Immunohistochemistry; D020935:MAP Kinase Signaling System / Q000502:physiology; D024510:Muscle Development; D018482:Muscle, Skeletal / Q000166:cytology / Q000196:embryology / Q000254:growth & development / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D020880:Neuregulins / Q000235:genetics / Q000378:metabolism*; D009469:Neuromuscular Junction / Q000502:physiology*; D010766:Phosphorylation; D011233:Precipitin Tests; D051381:Rats; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011950:Receptors, Cholinergic / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D014162:Transfection; D019076:Transgenes / Q000235:genetics
D051360:Cyclin-Dependent Kinase 5; D018844:Cyclin-Dependent Kinases; D009419:Nerve Tissue Proteins; D020880:Neuregulins; D018719:Erb-b2 Receptor Tyrosine Kinases; D011950:Receptors, Cholinergic; D011994:Recombinant Proteins; C089495:neuronal Cdk5 activator (p25-p35); C495907:Cdk5 protein, rat