Postsynaptic requirement for Abl kinases in assembly of the neuromuscular junction.
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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- Tyrosine
- Transfection
- Time Factors
- Synaptophysin
- Synapses
- Receptors, Cholinergic
- Receptor Protein-Tyrosine Kinases
- Radioimmunoassay
- Rabbits
- Pyrimidines
Citation
Published In
DOI
ISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Tyrosine
- Transfection
- Time Factors
- Synaptophysin
- Synapses
- Receptors, Cholinergic
- Receptor Protein-Tyrosine Kinases
- Radioimmunoassay
- Rabbits
- Pyrimidines