| First Author | Fu AK | Year | 2005 |
| Journal | Proc Natl Acad Sci U S A | Volume | 102 |
| Issue | 42 | Pages | 15224-9 |
| PubMed ID | 16203963 | Mgi Jnum | J:102479 |
| Mgi Id | MGI:3607648 | Doi | 10.1073/pnas.0507678102 |
| Citation | Fu AK, et al. (2005) Aberrant motor axon projection, acetylcholine receptor clustering, and neurotransmission in cyclin-dependent kinase 5 null mice. Proc Natl Acad Sci U S A 102(42):15224-9 |
| abstractText | Cyclin-dependent kinase (Cdk)5 is a key regulator of neural development. We have previously demonstrated that Cdk5/p35 are localized to the postsynaptic muscle and are implicated in the regulation of neuregulin/ErbB signaling in myotube culture. To further elucidate whether Cdk5 activity contributes to neuromuscular junction (NMJ) development in vivo, the NMJ of Cdk5-/- mice was examined. Consistent with our previous demonstration that Cdk5 phosphorylates ErbB2/3 to regulate its tyrosine phosphorylation, we report here that the phosphorylation of ErbB2 and ErbB3 and the ErbB2 kinase activity are reduced in Cdk5-deficient muscle. In addition, Cdk5-/- mice also display morphological abnormalities at the NMJ pre- and postsynaptically. Whereas the outgrowth of the main nerve trunk is grossly normal, the intramuscular nerve projections exhibit profuse and anomalous branching patterns in the Cdk5-/- embryos. The central band of acetylcholine receptor (AChR) clusters is also wider in Cdk5-/- diaphragms, together with the absence of S100 immunoreactivity along the phrenic nerve during late embryonic stages. Moreover, we unexpectedly discovered that the agrin-induced formation of large AChR clusters is significantly increased in primary muscle cultures prepared from Cdk5-null mice and in C2C12 myotubes when Cdk5 activity was suppressed. These abnormalities are accompanied by elevated frequency of miniature endplate potentials in Cdk5-null diaphragm. Taken together, our findings reveal the essential role of Cdk5 in regulating the development of motor axons and neuromuscular synapses in vivo. |
