Agrin-independent activation of the agrin signal transduction pathway.
The neural factor agrin induces the aggregation of acetylcholine receptors (AChRs) and other synaptic molecules on cultured myotubes. This aggregating activity can be mimicked by experimental manipulations that include treatment with neuraminidase or elevated calcium. We report evidence that neuraminidase and calcium act through the agrin signal transduction pathway. The effects of neuraminidase and calcium on AChR clustering are additive with that of agrin at low concentrations and cosaturating at high concentrations. In addition, like agrin, both neuraminidase and calcium cause rapid tyrosine phosphorylation of the muscle-specific kinase (MuSK) and the AChR-beta subunit. Our results argue that all three agents act directly on components of the same signal transduction complex. We suggest that sialic acids on components of the complex inhibit interactions necessary for signal transduction and that disinhibition can result in activation. In such a model, agrin could activate signal transduction by disinhibition or by circumventing the inhibition.
Grow
W A
WA
Department of Cell Biology and Anatomy, University of Arizona, Tucson, Arizona 85724-5044, USA.
Ferns
M
M
Gordon
H
H
D018171:Agrin / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects; D020013:Calcium Signaling / Q000502:physiology; D002449:Cell Aggregation / Q000187:drug effects; D002450:Cell Communication / Q000187:drug effects; D002478:Cells, Cultured; D018716:Molecular Mimicry / Q000187:drug effects; D009439:Neuraminidase / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D011505:Protein-Tyrosine Kinases / Q000187:drug effects; D011950:Receptors, Cholinergic / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects*
D018171:Agrin; D015220:Calcium Channels; D011950:Receptors, Cholinergic; D011505:Protein-Tyrosine Kinases; D009439:Neuraminidase; D002118:Calcium