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

Nature Neuroscience volume 4, pages 374381 (2001) | Download Citation

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Abstract

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.

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Acknowledgements

We thank Z. Wu for the myogenin cDNA plasmid, L. Mei for the ErbB2 and ErbB3 expression constructs and Y.P. Ching for advice. We thank P. Xie, R. Choi and K.C. Lok for technical assistance. This study was supported in part by grants from the Research Grants Council of Hong Kong to N.Y.I. (HKUST 2/99C, 6107/98M and 568/95M) and the Hong Kong Jockey Club. N.Y.I. was a recipient of the Croucher Foundation Senior Research Fellowship.

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    • Amy K. Y. Fu
    •  & Wing-Yu Fu

    The first two authors contributed equally to this work

Affiliations

  1. Department of Biochemistry, Biotechnology Research Institute, Molecular Neuroscience Center, Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, China

    • Amy K. Y. Fu
    • , Wing-Yu Fu
    • , Janet Cheung
    • , Fanny C. F. Ip
    • , Jerry H. Wang
    •  & Nancy Y. Ip
  2. Department of Biology, Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, China

    • Karl W. K. Tsim

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Correspondence to Nancy Y. Ip.

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DOI

https://doi.org/10.1038/86019