PMID- 11323662
OWN - NLM
STAT- MEDLINE
DCOM- 20010607
LR  - 20091119
IS  - 0028-0836 (Print)
IS  - 0028-0836 (Linking)
VI  - 410
IP  - 6832
DP  - 2001 Apr 26
TI  - Distinct roles of nerve and muscle in postsynaptic differentiation of the 
      neuromuscular synapse.
PG  - 1057-64
AB  - The development of chemical synapses is regulated by interactions between pre- 
      and postsynaptic cells. At the vertebrate skeletal neuromuscular junction, the 
      organization of an acetylcholine receptor (AChR)-rich postsynaptic apparatus has 
      been well studied. Much evidence suggests that the nerve-derived protein agrin 
      activates muscle-specific kinase (MuSK) to cluster AChRs through the 
      synapse-specific cytoplasmic protein rapsyn. But how postsynaptic differentiation 
      is initiated, or why most synapses are restricted to an 'end-plate band' in the 
      middle of the muscle remains unknown. Here we have used genetic methods to 
      address these issues. We report that the initial steps in postsynaptic 
      differentiation and formation of an end-plate band require MuSK and rapsyn, but 
      are not dependent on agrin or the presence of motor axons. In contrast, the 
      subsequent stages of synaptic growth and maintenance require nerve-derived agrin, 
      and a second nerve-derived signal that disperses ectopic postsynaptic apparatus.
FAU - Lin, W
AU  - Lin W
AD  - The Salk Institute, 10010 North Torrey Pines Road, La Jolla, California 92037, 
      USA.
FAU - Burgess, R W
AU  - Burgess RW
FAU - Dominguez, B
AU  - Dominguez B
FAU - Pfaff, S L
AU  - Pfaff SL
FAU - Sanes, J R
AU  - Sanes JR
FAU - Lee, K F
AU  - Lee KF
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Nature
JT  - Nature
JID - 0410462
RN  - 0 (Agrin)
RN  - 0 (Muscle Proteins)
RN  - 0 (Receptors, Cholinergic)
RN  - 0 (peripheral membrane protein 43K)
RN  - EC 2.7.10.1 (MUSK protein, human)
RN  - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases)
SB  - IM
MH  - Agrin/physiology
MH  - Animals
MH  - Axons/physiology
MH  - Cell Differentiation
MH  - Mice
MH  - Motor Neurons/*physiology
MH  - Muscle Development
MH  - Muscle Proteins/physiology
MH  - Muscle, Skeletal/embryology/growth & development/*physiology
MH  - Neuromuscular Junction/embryology/growth & development/*physiology
MH  - Receptor Protein-Tyrosine Kinases/physiology
MH  - Receptors, Cholinergic/physiology
MH  - Synapses/enzymology/*physiology
EDAT- 2001/04/27 10:00
MHDA- 2001/06/08 10:01
CRDT- 2001/04/27 10:00
PHST- 2001/04/27 10:00 [pubmed]
PHST- 2001/06/08 10:01 [medline]
PHST- 2001/04/27 10:00 [entrez]
AID - 35074025 [pii]
AID - 10.1038/35074025 [doi]
PST - ppublish
SO  - Nature. 2001 Apr 26;410(6832):1057-64. doi: 10.1038/35074025.