PMID- 22328506
OWN - NLM
STAT- MEDLINE
DCOM- 20130211
LR  - 20120424
IS  - 1477-9137 (Electronic)
IS  - 0021-9533 (Linking)
VI  - 125
IP  - Pt 6
DP  - 2012 Mar 15
TI  - Neuregulin-1 potentiates agrin-induced acetylcholine receptor clustering through 
      muscle-specific kinase phosphorylation.
PG  - 1531-43
LID - 10.1242/jcs.095109 [doi]
AB  - At neuromuscular synapses, neural agrin (n-agrin) stabilizes embryonic 
      postsynaptic acetylcholine receptor (AChR) clusters by signalling through the 
      muscle-specific kinase (MuSK) complex. Live imaging of cultured myotubes showed 
      that the formation and disassembly of primitive AChR clusters is a dynamic and 
      reversible process favoured by n-agrin, and possibly other synaptic signals. 
      Neuregulin-1 is a growth factor that can act through muscle ErbB receptor kinases 
      to enhance synaptic gene transcription. Recent studies suggest that 
      neuregulin-1-ErbB signalling can modulate n-agrin-induced AChR clustering 
      independently of its effects on transcription. Here we report that neuregulin-1 
      increased the size of developing AChR clusters when injected into muscles of 
      embryonic mice. We investigated this phenomenon using cultured myotubes, and 
      found that in the ongoing presence of n-agrin, neuregulin-1 potentiates AChR 
      clustering by increasing the tyrosine phosphorylation of MuSK. This potentiation 
      could be blocked by inhibiting Shp2, a postsynaptic tyrosine phosphatase known to 
      modulate the activity of MuSK. Our results provide new evidence that neuregulin-1 
      modulates the signaling activity of MuSK and hence might function as a 
      second-order regulator of postsynaptic AChR clustering at the neuromuscular 
      synapse. Thus two classic synaptic signalling systems (neuregulin-1 and n-agrin) 
      converge upon MuSK to regulate postsynaptic differentiation.
FAU - Ngo, Shyuan T
AU  - Ngo ST
AD  - School of Biomedical Sciences, University of Queensland, St. Lucia, 4072, 
      Queensland, Australia.
FAU - Cole, Rebecca N
AU  - Cole RN
FAU - Sunn, Nana
AU  - Sunn N
FAU - Phillips, William D
AU  - Phillips WD
FAU - Noakes, Peter G
AU  - Noakes PG
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120210
PL  - England
TA  - J Cell Sci
JT  - Journal of cell science
JID - 0052457
RN  - 0 (Agrin)
RN  - 0 (Neuregulin-1)
RN  - 0 (Nrg1 protein, mouse)
RN  - 0 (Receptors, Cholinergic)
RN  - EC 2.7.10.1 (MuSK protein, mouse)
RN  - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases)
SB  - IM
MH  - Agrin/*physiology
MH  - Animals
MH  - Cell Differentiation/physiology
MH  - Cell Line
MH  - Female
MH  - Humans
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Myoblasts/cytology/enzymology
MH  - Neuregulin-1/*physiology
MH  - Phosphorylation/physiology
MH  - Pregnancy
MH  - Primary Cell Culture
MH  - Rats
MH  - Receptor Protein-Tyrosine Kinases/*metabolism
MH  - Receptors, Cholinergic/*metabolism
EDAT- 2012/02/14 06:00
MHDA- 2013/02/12 06:00
CRDT- 2012/02/14 06:00
PHST- 2012/02/14 06:00 [entrez]
PHST- 2012/02/14 06:00 [pubmed]
PHST- 2013/02/12 06:00 [medline]
AID - jcs.095109 [pii]
AID - 10.1242/jcs.095109 [doi]
PST - ppublish
SO  - J Cell Sci. 2012 Mar 15;125(Pt 6):1531-43. doi: 10.1242/jcs.095109. Epub 2012 Feb 
      10.