Calcium-dependent maintenance of agrin-induced postsynaptic specializations

Although much progress has been made in understanding synapse formation, little is known about the mechanisms underlying synaptic maintenance and loss. The formation of agrin-induced AChR clusters on cultured myotubes requires both activation of the receptor tyrosine kinase MuSK and intracellular ca...

Full description

Saved in:
Bibliographic Details
Published in:Neuroscience 2003, Vol.122 (3), p.659-668
Main Authors: Megeath, L.J, Kirber, M.T, Hopf, C, Hoch, W, Fallon, J.R
Format: Article
Language:English
Subjects:
Acetylcholine - pharmacology
acetylcholine receptor
Agrin - metabolism
Agrin - pharmacology
Animals
Biological and medical sciences
Blotting, Western
Bungarotoxins - metabolism
Calcium - metabolism
Cell physiology
Cells, Cultured
Chelating Agents - pharmacology
Chick Embryo
Dose-Response Relationship, Drug
Drug Interactions
Egtazic Acid - analogs & derivatives
Egtazic Acid - pharmacology
Enzyme Inhibitors - pharmacology
Extracellular Space - metabolism
Fundamental and applied biological sciences. Psychology
Fura-2 - metabolism
Intracellular Space - metabolism
Miscellaneous
Molecular and cellular biology
Muscle Fibers, Skeletal
MuSK
neuromuscular junction
Phosphorylation
Protein Binding
Rats
Receptor Aggregation - drug effects
Receptor Protein-Tyrosine Kinases - metabolism
Receptors, Cholinergic - drug effects
Receptors, Cholinergic - metabolism
Synapses - drug effects
Time Factors
Vanadates - pharmacology
Vasodilator Agents - pharmacology
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Although much progress has been made in understanding synapse formation, little is known about the mechanisms underlying synaptic maintenance and loss. The formation of agrin-induced AChR clusters on cultured myotubes requires both activation of the receptor tyrosine kinase MuSK and intracellular calcium fluxes. Here, we provide evidence that such AChR clusters are maintained by agrin/MuSK-induced intracellular calcium fluxes. Clamping intracellular calcium fluxes after AChR clusters have formed leads to rapid MuSK and AChR tyrosine dephosphorylation and cluster dispersal, even in the continued presence of agrin. Both the dephosphorylation and the dispersal are inhibited by the tyrosine phosphatase inhibitor pervanadate. In contrast, clamping intracellular calcium at the time of initial agrin stimulation has no effect on agrin-induced MuSK or AChR phosphorylation, but blocks AChR cluster formation. These findings suggest an avenue by which postsynaptic stability can be regulated by modification of intracellular signaling pathways that are distinct from those used during synapse formation.
ISSN:0306-4522
1873-7544
DOI:10.1016/S0306-4522(03)00602-X