The Ig1/2 Domain of MuSK Binds to Muscle Surface and Is Involved in Acetylcholine Receptor Clustering

Vol. 16, No. 2-3, 2008

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Paper

The Ig1/2 Domain of MuSK Binds to Muscle Surface and Is Involved in Acetylcholine Receptor Clustering
Qiang Wang^{a, b}, Bin Zhang^a, Ye Elaine Wang^a, Wen-Cheng Xiong^a, Lin Mei^a

^aProgram of Developmental Neurobiology, Institute of Molecular Medicine and Genetics and Department of Neurology, Medical College of Georgia, Augusta, Ga., and
^bDepartment of Neuroscience, Johns Hopkins University, Baltimore, Md., USA

Address of Corresponding Author

Neurosignals 2008;16:246-253 (DOI: 10.1159/000111567)

Key Words

MuSK
Ectodomain
Agrin
Acetylcholine receptor
Binding
Neuromuscular junction

Abstract

The neuromuscular junction, the synapse between motor neurons and muscle cells, serves as an excellent model for studying synapse formation. Agrin is believed to be released by motor neurons to induce postsynaptic differentiation at the neuromuscular junction. MuSK, a receptor tyrosine kinase, appears to be a key component of the agrin receptor complex. However, how agrin activates MuSK remains unclear. To address this question, we characterized the binding of the MuSK extracellular region to the muscle cell surface. The MuSK ectodomain was found to bind to muscle cells in a manner dependent on stimulation with neural agrin. Moreover, the binding was myotube specific and appeared to be mediated by two regions in the MuSK: one region containing the first and second immunoglobin domains and the other containing the cysteine-rich domain. Importantly, recombinant proteins containing the binding activity can block full-length MuSK binding to muscle cells and agrin-induced AChR clustering. These results suggest that the Ig1/2 domain of MuSK is involved in AChR clustering by binding to the muscle surface.

Author Contacts

Dr. Lin Mei
Program of Developmental Neurobiology
Institute of Molecular Medicine and Genetics and Department of Neurology
Medical College of Georgia, 1120 15th Street, Augusta, GA 30912 (USA)
Tel. +1 706 721 8775, Fax +1 706 721 8685, E-Mail lmei@mcg.edu

Article Information

Q.W. and B.Z. contributed equally.

Published online: February 5, 2008
Number of Print Pages : 8
Number of Figures : 5, Number of Tables : 0, Number of References : 30

Medline Abstract (ID 18253062)

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