Localization and regulation of MuSK at the neuromuscular junction

David C. Bowen, John S. Park, Sue Bodine, Jennifer L. Stark, David M. Valenzuela, Trevor N. Stitt, George D. Yancopoulos, Ronald M. Lindsay, David J. Glass, Peter S. Distefano

Research output: Contribution to journalArticle

65 Citations (Scopus)

Abstract

The receptor tyrosine kinase, MuSK, is required for the formation of the neuromuscular junction (NMJ) where MuSK becomes phosphorylated when exposed to neuronally synthesized isoforms of agrin. To understand better the mechanisms by which MuSK mediates the formation of the NMJ, we have examined how MuSK expression is regulated during development in the embryo, by neuromuscular injury in the adult and by agrin in vitro. Here we show that MuSK is associated with the earliest observable AChR clusters at the developing motor endplate and that MuSK and AChRs codistribute throughout the development of the NMJ. These two proteins are also coordinately regulated on the surfaces of cultured myotubes where MuSK and AChRs colocalize both in spontaneous and agrin-induced clusters. While MuSK is normally restricted to the motor endplate in adult muscle, denervation results in its extrajunctional expression, although a discernible concentration of MuSK remains localized to the motor endplate even 14 days after denervation. Extrajunctional MuSK is first apparent 3 days after denervation and is sharply reduced upon reinnervation. Muscle paralysis also markedly alters the expression of MuSK in adult muscle and results in increased expression of MuSK as well as increased transcription of MuSK mRNA by extrasynaptic myonuclei. Together, these findings demonstrate that MuSK expression is highly regulated by innervation, muscle activity, and agrin, while the distribution of MuSK is precisely coordinated with that of the AChR.

Original languageEnglish (US)
Pages (from-to)309-319
Number of pages11
JournalDevelopmental Biology
Volume199
Issue number2
DOIs
StatePublished - Jul 15 1998
Externally publishedYes

Fingerprint

Agrin
Neuromuscular Junction
Motor Endplate
Denervation
Muscles
Muscle Denervation
Skeletal Muscle Fibers
Receptor Protein-Tyrosine Kinases
Paralysis
Embryonic Development
Protein Isoforms
Messenger RNA
Wounds and Injuries
Proteins

ASJC Scopus subject areas

  • Developmental Biology

Cite this

Bowen, D. C., Park, J. S., Bodine, S., Stark, J. L., Valenzuela, D. M., Stitt, T. N., ... Distefano, P. S. (1998). Localization and regulation of MuSK at the neuromuscular junction. Developmental Biology, 199(2), 309-319. https://doi.org/10.1006/dbio.1998.8936

Localization and regulation of MuSK at the neuromuscular junction. / Bowen, David C.; Park, John S.; Bodine, Sue; Stark, Jennifer L.; Valenzuela, David M.; Stitt, Trevor N.; Yancopoulos, George D.; Lindsay, Ronald M.; Glass, David J.; Distefano, Peter S.

In: Developmental Biology, Vol. 199, No. 2, 15.07.1998, p. 309-319.

Research output: Contribution to journalArticle

Bowen, DC, Park, JS, Bodine, S, Stark, JL, Valenzuela, DM, Stitt, TN, Yancopoulos, GD, Lindsay, RM, Glass, DJ & Distefano, PS 1998, 'Localization and regulation of MuSK at the neuromuscular junction', Developmental Biology, vol. 199, no. 2, pp. 309-319. https://doi.org/10.1006/dbio.1998.8936
Bowen DC, Park JS, Bodine S, Stark JL, Valenzuela DM, Stitt TN et al. Localization and regulation of MuSK at the neuromuscular junction. Developmental Biology. 1998 Jul 15;199(2):309-319. https://doi.org/10.1006/dbio.1998.8936
Bowen, David C. ; Park, John S. ; Bodine, Sue ; Stark, Jennifer L. ; Valenzuela, David M. ; Stitt, Trevor N. ; Yancopoulos, George D. ; Lindsay, Ronald M. ; Glass, David J. ; Distefano, Peter S. / Localization and regulation of MuSK at the neuromuscular junction. In: Developmental Biology. 1998 ; Vol. 199, No. 2. pp. 309-319.
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