Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Site Tools

  • AAAS
  • Subscribe
  • Feedback

Site Search

Search Advanced

Science 23 June 2006:
Vol. 312. no. 5781, pp. 1802 - 1805
DOI: 10.1126/science.1127142
Prev | Table of Contents | Next

Reports

The Muscle Protein Dok-7 Is Essential for Neuromuscular Synaptogenesis

Kumiko Okada,1* Akane Inoue,1* Momoko Okada,1 Yoji Murata,1 Shigeru Kakuta,3 Takafumi Jigami,4 Sachiko Kubo,3 Hirokazu Shiraishi,5 Katsumi Eguchi,5 Masakatsu Motomura,5 Tetsu Akiyama,4 Yoichiro Iwakura,3 Osamu Higuchi,1{dagger} Yuji Yamanashi1,2{dagger}

The formation of the neuromuscular synapse requires muscle-specific receptor kinase (MuSK) to orchestrate postsynaptic differentiation, including the clustering of receptors for the neurotransmitter acetylcholine. Upon innervation, neural agrin activates MuSK to establish the postsynaptic apparatus, although agrin-independent formation of neuromuscular synapses can also occur experimentally in the absence of neurotransmission. Dok-7, a MuSK-interacting cytoplasmic protein, is essential for MuSK activation in cultured myotubes; in particular, the Dok-7 phosphotyrosine-binding domain and its target in MuSK are indispensable. Mice lacking Dok-7 formed neither acetylcholine receptor clusters nor neuromuscular synapses. Thus, Dok-7 is essential for neuromuscular synaptogenesis through its interaction with MuSK.

1 Department of Cell Regulation, Medical Research Institute, Tokyo Medical and Dental University, Tokyo 113–8510, Japan.
2 School of Biomedical Science, Tokyo Medical and Dental University, Tokyo 113–8510, Japan.
3 Center for Experimental Medicine, Institute of Medical Science, University of Tokyo, Tokyo 108–8639, Japan.
4 Laboratory of Molecular and Genetic Information, Institute of Molecular and Cellular Biosciences, University of Tokyo, Tokyo 113–0032, Japan.
5 The First Department of Internal Medicine, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852–8501, Japan.

* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: yamanashi.creg{at}mri.tmd.ac.jp (Y.Y.); higuchi.creg{at}mri.tmd.ac.jp (O.H.)

Read the Full Text

ADVERTISEMENT
Click Me!

ADVERTISEMENT
Click Me!

To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)