UMMS Affiliation

Department of Cell Biology

Publication Date

2-7-1998

Document Type

Article

Subjects

Agrin; Animals; Calcium; Chelating Agents; Chick Embryo; Egtazic Acid; Phosphorylation; *Receptor Aggregation; Receptors, Cholinergic; Signal Transduction

Disciplines

Life Sciences | Medicine and Health Sciences

Abstract

Agrin is an extracellular matrix protein that directs neuromuscular junction formation. Early signal transduction events in agrin-mediated postsynaptic differentiation include activation of a receptor tyrosine kinase and phosphorylation of acetylcholine receptors (AChRs), but later steps in this pathway are unknown. Here, we have investigated the role of intracellular calcium in agrin-induced AChR clustering on cultured myotubes. Clamping intracellular calcium levels by loading with the fast chelator BAPTA inhibited agrin-induced AChR aggregation. In addition, preexisting AChR aggregates dispersed under these conditions, indicating that the maintenance of AChR clusters is similarly dependent on intracellular calcium fluxes. The decrease in AChR clusters in BAPTA-loaded cells was dose-dependent and reversible, and no change in the number or mobility of AChRs was observed. Clamping intracellular calcium did not block agrin-induced tyrosine phosphorylation of the AChR beta-subunit, indicating that intracellular calcium fluxes are likely to act downstream from or parallel to AChR phosphorylation. Finally, the targets of the intracellular calcium are likely to be close to the calcium source, since agrin-induced AChR clustering was unaffected in cells loaded with EGTA, a slower-binding calcium chelator. These findings distinguish a novel step in the signal transduction mechanism of agrin and raise the possibility that the pathways mediating agrin- and activity-driven changes in synaptic architecture could intersect at the level of intracellular calcium fluxes.

Rights and Permissions

Citation: J Neurosci. 1998 Jan 15;18(2):672-8.

Related Resources

Link to Article in PubMed

Journal/Book/Conference Title

The Journal of neuroscience : the official journal of the Society for Neuroscience

PubMed ID

9425009

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