Receptor tyrosine kinase specific for the skeletal muscle lineage: Expression in embryonic muscle, at the neuromuscular junction, and after injury

David M. Valenzuela, Trevor N. Stitt, Peter S. DiStefano, Eduardo Rojas, Karen Mattsson, Debra L. Compton, Lorna Nunez, John S. Park, Jennifer L. Stark, David R. Gies, Susan Thomas, Michelle M. Le Beau, Anthony A. Fernald, Neal G. Copeland, Nancy A. Jenkins, Steven J. Burden, David J. Glass, George D. Yancopoulos

Research output: Contribution to journalArticle

338 Scopus citations

Abstract

While a number of growth factors have been described that are highly specific for particular cell lineages, neither a factor nor a receptor uniquely specific to the skeletal muscle lineage has previously been described. Here we identify a receptor tyrosine kinase (RTK) specific to skeletal muscle, which we term "MuSK" for muscle-specific kinase. MuSK is expressed at low levels in proliferating myoblasts and is induced upon differentiation and fusion. In the embryo, it is specifically expressed in early myotomes and developing muscle. MuSK is then dramatically down-regulated in mature muscle, where it remains prominent only at the neuromuscular junction; MuSK is thus the only known RTK that localizes to the neuromuscular junction. Strikingly, MuSK expression is dramatically induced throughout the adult myofiber after denervation, block of electrical activity, or physical immobilization. In humans, MuSK maps to chromosome 9g31.3-32, which overlaps with the region reported to contain the Fukuyama muscular dystrophy mutation. Identification of MuSK introduces a novel receptor-factor system that seems sure to play an important and selective role in many aspects of skeletal muscle development and function.

Original languageEnglish (US)
Pages (from-to)573-584
Number of pages12
JournalNeuron
Volume15
Issue number3
DOIs
StatePublished - Sep 1995

ASJC Scopus subject areas

  • Neuroscience(all)

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