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Journal Article

MuSK induces in vivo acetylcholine receptor clusters in a ligand-independent mannerr

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Sander,  Andreas
Department of Cell Physiology, Max Planck Institute for Medical Research, Max Planck Society;

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Hesser,  Boris
Department of Cell Physiology, Max Planck Institute for Medical Research, Max Planck Society;

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Witzemann,  Veit
Department of Molecular Neurobiology, Max Planck Institute for Medical Research, Max Planck Society;
Department of Cell Physiology, Max Planck Institute for Medical Research, Max Planck Society;

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Citation

Sander, A., Hesser, B., & Witzemann, V. (2001). MuSK induces in vivo acetylcholine receptor clusters in a ligand-independent mannerr. Journal of Cell Biology, 155(7), 1287-1296. doi:10.1083/jcb.200105034.


Cite as: http://hdl.handle.net/11858/00-001M-0000-0028-FF95-0
Abstract
Muscle-specific receptor tyrosine kinase (MuSK) is required for the formation of the neuromuscular junction. Using direct gene transfer into single fibers, MuSK was expressed extrasynaptically in innervated rat muscle in vivo to identify its contribution to synapse formation. Spontaneous MuSK kinase activity leads, in the absence of its putative ligand neural agrin, to the appearance of epsilon-subunit-specific transcripts, the formation of acetylcholine receptor clusters, and acetylcholinesterase aggregates. Expression of kinase-inactive MuSK did not result in the formation of acetylcholine receptor (AChR) clusters, whereas a mutant MuSK lacking the ectodomain did induce AChR clusters. The contribution of endogenous MuSK was excluded by using genetically altered mice, where the kinase domain of the MuSK gene was flanked by loxP sequences and could be deleted upon expression of Cre recombinase. This allowed the conditional inactivation of endogenous MuSK in single muscle fibers and prevented the induction of ectopic AChR clusters. Thus, the kinase activity of MuSK initiates signals that are sufficient to induce the formation of AChR clusters. This process does not require additional determinants located in the ectodomain.