PMID- 10741468
OWN - NLM
STAT- MEDLINE
DCOM- 20000525
LR  - 20190720
IS  - 0302-766X (Print)
IS  - 0302-766X (Linking)
VI  - 299
IP  - 2
DP  - 2000 Feb
TI  - Sialic acid inhibits agrin signaling in C2 myotubes.
PG  - 273-9
AB  - Acetylcholine receptor (AChR) clustering is an early event in neuromuscular 
      synapse formation that is commonly studied using muscle cell culture. Motor 
      neuron-derived agrin induces the postsynaptic tyrosine phosphorylation of both a 
      muscle-specific kinase (MuSK) and the AChR beta-subunit. These phosphorylation 
      events are required for AChR clustering, suggesting an agrin-driven signaling 
      pathway. Both the phosphorylation events and AChR clustering can also be induced 
      by neuraminidase, an enzyme that cleaves sialic acid from glycoconjugates, 
      suggesting that neuraminidase is able to activate the agrin signaling pathway. A 
      postulated signal for postsynaptic differentiation at sites of nerve-muscle 
      contact during vertebrate development is the enzymatic removal of basal lamina 
      components. We show here that bath-applied sialic acid has an effect directly 
      opposite that of agrin or neuraminidase. Sialic acid not only decreases AChR 
      clustering but also diminishes the tyrosine phosphorylation of MuSK and the AChR 
      beta-subunit signal-transduction events normally driven by agrin. However, sialic 
      acid does not prevent agrin-binding molecules from colocalizing with the 
      decreased number of AChR clusters that do form, suggesting that sialic acid is 
      acting to inhibit the agrin signaling pathway downstream of agrin binding to the 
      muscle cell membrane. We propose a regulatory role for sialic acid in the signal 
      transduction events of neuromuscular synapse formation, in which agrin or 
      neuraminidase can overcome this sialic acid repression, resulting in the 
      clustering of AChRs and other postsynaptic molecules.
FAU - Grow, W A
AU  - Grow WA
AD  - Department of Cell Biology and Anatomy, College of Medicine, University of 
      Arizona, Tucson 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.
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - Germany
TA  - Cell Tissue Res
JT  - Cell and tissue research
JID - 0417625
RN  - 0 (Agrin)
RN  - 0 (Receptors, Cholinergic)
RN  - EC 2.7.10.1 (MUSK protein, human)
RN  - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases)
RN  - EC 3.2.1.18 (Neuraminidase)
RN  - GZP2782OP0 (N-Acetylneuraminic Acid)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Agrin/*antagonists & inhibitors/pharmacology
MH  - Animals
MH  - Calcium/pharmacology
MH  - Cell Differentiation/drug effects
MH  - Cells, Cultured
MH  - Muscle Fibers, Skeletal/*drug effects/metabolism
MH  - N-Acetylneuraminic Acid/*pharmacology
MH  - Neuraminidase/pharmacology
MH  - Neuromuscular Junction/*drug effects/metabolism
MH  - Phosphorylation/drug effects
MH  - Protein Processing, Post-Translational/*drug effects
MH  - Receptor Aggregation/drug effects
MH  - Receptor Protein-Tyrosine Kinases/metabolism
MH  - Receptors, Cholinergic/*metabolism
MH  - Signal Transduction/*drug effects
EDAT- 2000/03/31 09:00
MHDA- 2000/06/08 09:00
CRDT- 2000/03/31 09:00
PHST- 2000/03/31 09:00 [pubmed]
PHST- 2000/06/08 09:00 [medline]
PHST- 2000/03/31 09:00 [entrez]
AID - 10.1007/s004419900146 [doi]
PST - ppublish
SO  - Cell Tissue Res. 2000 Feb;299(2):273-9. doi: 10.1007/s004419900146.