PMID- 18567849
OWN - NLM
STAT- MEDLINE
DCOM- 20080908
LR  - 20080623
IS  - 0077-8923 (Print)
IS  - 0077-8923 (Linking)
VI  - 1132
DP  - 2008
TI  - Cell-to-cell signaling at the neuromuscular junction: the dynamic role of the 
      extracellular matrix.
PG  - 13-8
LID - 10.1196/annals.1405.035 [doi]
AB  - The extracellular matrix at the neuromuscular junction plays many roles. The 
      matrix plays a structural role in that it maintains the spatial relationship 
      between the muscle cell, Schwann cell, and presynaptic motor neuron. The matrix 
      also plays a role in cell-to-cell signaling. The most studied member of this 
      group is the heparan sulfate proteoglycan, agrin. Agrin is an integral member of 
      the synaptic matrix, and it plays the pivotal role of instructing the muscle cell 
      to aggregate acetylcholine receptors (AChRs) to the synapse. Agrin is released by 
      the motor neuron, where it binds stably to the extracellular matrix. Agrin 
      interacts with the muscle-specific tyrosine kinase (MuSK). Mice that lack agrin, 
      or MuSK, fail to form neuromuscular junctions. Thus, the extracellular matrix is 
      critical to both the structure and function of the neuromuscular junction. 
      Remodeling of the extracellular matrix at the neuromuscular junction is needed to 
      maintain stability, to allow growth, or to destabilize and remove synapses. 
      Matrix metalloproteinases are key regulators of the extracellular matrix. In 
      particular, matrix metalloproteinase 3 (MMP3) has been implicated in regulation 
      of synaptic structure. MMP3 cleaves agrin. Antibodies to MMP3 recognize molecules 
      concentrated at the synapses of frog neuromuscular junctions. Neuromuscular 
      junctions in MMP3 null mutant mice have increased junctional folds, and AChR 
      aggregates. Changes in synaptic activity will alter the activity of MMP3 at the 
      synapse. Thus, the extracellular matrix is critical to the formation of the 
      synapse, and synaptic activity controls the structure and function of the 
      molecules in the extracellular matrix.
FAU - Werle, Michael J
AU  - Werle MJ
AD  - Department of Anatomy and Cell Biology, University of Kansas Medical Center, 
      Kansas City, KS 66160, USA. Mwerle@kumc.edu
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Ann N Y Acad Sci
JT  - Annals of the New York Academy of Sciences
JID - 7506858
RN  - EC 3.4.24.17 (Matrix Metalloproteinase 3)
SB  - IM
MH  - Animals
MH  - *Cell Communication
MH  - Extracellular Matrix/*metabolism
MH  - Humans
MH  - Matrix Metalloproteinase 3/genetics/metabolism
MH  - Neuromuscular Junction/*metabolism
MH  - *Signal Transduction
EDAT- 2008/06/24 09:00
MHDA- 2008/09/09 09:00
CRDT- 2008/06/24 09:00
PHST- 2008/06/24 09:00 [pubmed]
PHST- 2008/09/09 09:00 [medline]
PHST- 2008/06/24 09:00 [entrez]
AID - 1132/1/13 [pii]
AID - 10.1196/annals.1405.035 [doi]
PST - ppublish
SO  - Ann N Y Acad Sci. 2008;1132:13-8. doi: 10.1196/annals.1405.035.