Source of Synapse Kinase Activity Discovered

Researchers studying the development of the nervous system have found 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.

Investigators from Duke University Medical Center (Durham, NC, USA) used antibodies that could detect the Abl and Arg kinases to show in slices of mouse muscle tissue that the kinases were localized to the postsynaptic neuromuscular junction. They also showed that inhibiting Abl and Arg in cell cultures of mouse muscle cells inhibited the ability of acetylcholine receptor clusters to form. In further experiments with cell cultures, the researchers demonstrated that agrin triggers Abl and MuSK to form a specific interacting complex with one another that triggers the signaling required for receptor clusters to form. These findings were published June 8, 2003, in the online edition of Nature Neuroscience.

"If it should prove that neuromuscular diseases can be linked to defects in this pathway, it might be feasible to use drugs to modulate that pathway by affecting the Abl kinases or their targets to treat the disease,” said senior author Dr. Anne Marie Pendergast, associate professor of pharmacology and cancer biology at Duke University. "And, of course, the more you know about the pathway, the better you are equipped for such pharmacological intervention. These studies also raise a caution about giving compounds that inhibit Abl function, particularly during development, because the formation of the nervous system requires functional Abl kinases.”




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