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PMID:7546737

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Citation

Valenzuela, DM, Stitt, TN, DiStefano, PS, Rojas, E, Mattsson, K, Compton, DL, Nuñez, L, Park, JS, Stark, JL and Gies, DR (1995) Receptor tyrosine kinase specific for the skeletal muscle lineage: expression in embryonic muscle, at the neuromuscular junction, and after injury. Neuron 15:573-84

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 9q31.3-32, 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.

Links

PubMed

Keywords

Amino Acid Sequence; Animals; Blotting, Northern; Chromosome Mapping; Chromosomes, Human, Pair 9; Cloning, Molecular; Conserved Sequence; Gene Expression; Humans; Mice; Molecular Sequence Data; Muscle Denervation; Muscle, Skeletal/embryology; Muscle, Skeletal/enzymology; Neuromuscular Junction/enzymology; Polymerase Chain Reaction; RNA, Messenger/biosynthesis; Rats; Receptor Protein-Tyrosine Kinases/chemistry; Receptor Protein-Tyrosine Kinases/genetics; Receptor Protein-Tyrosine Kinases/metabolism; Receptors, Cholinergic/analysis; Synapses/enzymology

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:MUSK

involved_in

GO:0007169: transmembrane receptor protein tyrosine kinase signaling pathway

ECO:0000304: author statement supported by traceable reference used in manual assertion

P

Seeded From UniProt

complete

RAT:MUSK

involved_in

GO:0007528: neuromuscular junction development

ECO:0000270: expression pattern evidence used in manual assertion

P

Seeded From UniProt

complete

RAT:MUSK

GO:0004714: transmembrane receptor protein tyrosine kinase activity

ECO:0000314:

F

Figure 1 shows a Northern blot analysis of MuSK expression in adult rat tissue and during early postnatal development of the rat gastrocnemius skeletal muscle.

complete

See also

References

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