PMID- 10712627
OWN - NLM
STAT- MEDLINE
DCOM- 20000525
LR  - 20190815
IS  - 0953-816X (Print)
IS  - 0953-816X (Linking)
VI  - 12
IP  - 2
DP  - 2000 Feb
TI  - Acetylcholine receptors are required for postsynaptic aggregation driven by the 
      agrin signalling pathway.
PG  - 467-72
AB  - To investigate the role of acetylcholine receptors (AChRs) in the aggregation of 
      postsynaptic molecules on muscle cells, we utilized the 1R- genetic variant of C2 
      muscle cells which has very little expression of AChRs in its cell membrane. On 
      C2 myotubes, AChRs cluster spontaneously, with the frequency of clustering 
      greatly enhanced by motor neuron-derived agrin. Signal transduction events driven 
      by agrin, including the tyrosine phosphorylation of muscle-specific kinase (MuSK) 
      and the AChR beta subunit, have been implicated as requirements of postsynaptic 
      scaffold assembly. We show here that some molecules of the postsynaptic scaffold 
      spontaneously aggregate and colocalize on 1R- myotubes at very low frequency, 
      including an as yet unidentified agrin binding molecule, beta-dystroglycan and 
      MuSK. Agrin is unable to increase the frequency of these aggregations, but does 
      cause tyrosine phosphorylation of MuSK. We conclude that free molecules can 
      associate into aggregates independently of AChRs, but AChRs are required for 
      high-frequency molecular aggregation driven by the agrin signalling pathway. MuSK 
      tyrosine phosphorylation appears to precede a requisite event involving AChRs 
      that aggregates postsynaptic molecules.
FAU - Grow, W A
AU  - Grow WA
AD  - Department of Cell Biology & Anatomy, College of Medicine, University of Arizona, 
      Tucson, Arizona 85724-5044, USA. wgrow@online.emich.edu
FAU - Gordon, H
AU  - Gordon H
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PL  - France
TA  - Eur J Neurosci
JT  - The European journal of neuroscience
JID - 8918110
RN  - 0 (Agrin)
RN  - 0 (Cytoskeletal Proteins)
RN  - 0 (DAG1 protein, human)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Muscle Proteins)
RN  - 0 (Receptors, Cholinergic)
RN  - 146888-27-9 (Dystroglycans)
RN  - EC 2.7.10.1 (MUSK protein, human)
RN  - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases)
SB  - IM
MH  - Agrin/pharmacology/*physiology
MH  - Animals
MH  - Cells, Cultured
MH  - Cytoskeletal Proteins/metabolism
MH  - Dystroglycans
MH  - Membrane Glycoproteins/metabolism
MH  - Microscopy, Fluorescence
MH  - Muscle Proteins/*physiology
MH  - Muscle, Skeletal/cytology/drug effects
MH  - Phosphorylation
MH  - Protein Processing, Post-Translational
MH  - Receptor Aggregation/drug effects/*physiology
MH  - Receptor Protein-Tyrosine Kinases/metabolism
MH  - Receptors, Cholinergic/deficiency/*physiology
MH  - Signal Transduction/*physiology
MH  - Stem Cells/cytology/drug effects
EDAT- 2000/03/11 09:00
MHDA- 2000/06/08 09:00
CRDT- 2000/03/11 09:00
PHST- 2000/03/11 09:00 [pubmed]
PHST- 2000/06/08 09:00 [medline]
PHST- 2000/03/11 09:00 [entrez]
AID - ejn923 [pii]
AID - 10.1046/j.1460-9568.2000.00923.x [doi]
PST - ppublish
SO  - Eur J Neurosci. 2000 Feb;12(2):467-72. doi: 10.1046/j.1460-9568.2000.00923.x.