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Postsynaptic requirement for Abl kinases in assembly of the neuromuscular junction.

Publication ,  Journal Article
Finn, AJ; Feng, G; Pendergast, AM
Published in: Nat Neurosci
July 2003

Agrin signals through the muscle-specific receptor tyrosine kinase (MuSK) to cluster acetylcholine receptors (AChRs) on the postsynaptic membrane of the neuromuscular junction (NMJ). This stands as the prevailing model of synapse induction by a presynaptic factor, yet the agrin-dependent MuSK signaling cascade is largely undefined. Abl1 (previously known as Abl) and the Abl1-related gene product Abl2 (previously known as Arg) define a family of tyrosine kinases that regulate actin structure and presynaptic axon guidance. Here we show that the Abl kinases are critical mediators of postsynaptic assembly downstream of agrin and MuSK. In mouse muscle, Abl kinases were localized to the postsynaptic membrane of the developing NMJ. In cultured myotubes, Abl kinase activity was required for agrin-induced AChR clustering and enhancement of MuSK tyrosine phosphorylation. Moreover, MuSK and Abl kinases effected reciprocal tyrosine phosphorylation and formed a complex after agrin engagement. Our findings suggest that Abl kinases provide the developing synapse with the kinase activity required for signal amplification and the intrinsic cytoskeletal regulatory capacity required for assembly and remodeling.

Duke Scholars

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Published In

Nat Neurosci

DOI

ISSN

1097-6256

Publication Date

July 2003

Volume

6

Issue

7

Start / End Page

717 / 723

Location

United States

Related Subject Headings

  • Tyrosine
  • Transfection
  • Time Factors
  • Synaptophysin
  • Synapses
  • Receptors, Cholinergic
  • Receptor Protein-Tyrosine Kinases
  • Radioimmunoassay
  • Rabbits
  • Pyrimidines
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Finn, A. J., Feng, G., & Pendergast, A. M. (2003). Postsynaptic requirement for Abl kinases in assembly of the neuromuscular junction. Nat Neurosci, 6(7), 717–723. https://doi.org/10.1038/nn1071
Finn, Alexander J., Guoping Feng, and Ann Marie Pendergast. “Postsynaptic requirement for Abl kinases in assembly of the neuromuscular junction.Nat Neurosci 6, no. 7 (July 2003): 717–23. https://doi.org/10.1038/nn1071.
Finn AJ, Feng G, Pendergast AM. Postsynaptic requirement for Abl kinases in assembly of the neuromuscular junction. Nat Neurosci. 2003 Jul;6(7):717–23.
Finn, Alexander J., et al. “Postsynaptic requirement for Abl kinases in assembly of the neuromuscular junction.Nat Neurosci, vol. 6, no. 7, July 2003, pp. 717–23. Pubmed, doi:10.1038/nn1071.
Finn AJ, Feng G, Pendergast AM. Postsynaptic requirement for Abl kinases in assembly of the neuromuscular junction. Nat Neurosci. 2003 Jul;6(7):717–723.

Published In

Nat Neurosci

DOI

ISSN

1097-6256

Publication Date

July 2003

Volume

6

Issue

7

Start / End Page

717 / 723

Location

United States

Related Subject Headings

  • Tyrosine
  • Transfection
  • Time Factors
  • Synaptophysin
  • Synapses
  • Receptors, Cholinergic
  • Receptor Protein-Tyrosine Kinases
  • Radioimmunoassay
  • Rabbits
  • Pyrimidines