PMID- 15044844
OWN - NLM
STAT- MEDLINE
DCOM- 20040811
LR  - 20071114
IS  - 0300-4864 (Print)
IS  - 0300-4864 (Linking)
VI  - 32
IP  - 9
DP  - 2003 Nov
TI  - Structural alterations at the neuromuscular junctions of matrix metalloproteinase 
      3 null mutant mice.
PG  - 1129-42
AB  - Matrix metalloproteinases are important regulators of extracellular matrix 
      molecules and cell-cell signaling. Antibodies to matrix metalloproteinase 3 
      (MMP3) recognize molecules at the frog neuromuscular junction, and MMP3 can 
      remove agrin from synaptic basal lamina (VanSaun & Werle, 2000). To gain insight 
      into the possible roles of MMP3 at the neuromuscular junction, detailed 
      observations were made on the structure and function of the neuromuscular 
      junctions in MMP3 null mutant mice. Striking differences were found in the 
      appearance of the postsynaptic apparatus of MMP3 null mutant mice. Endplates had 
      an increased volume of AChR stained regions within the endplate structure, 
      leaving only small regions devoid of AChRs. Individual postsynaptic gutters were 
      wider, containing prominent lines that represent the AChRs concentrated at the 
      tops of the junctional folds. Electron microscopy revealed a dramatic increase in 
      the number and size of the junctional folds, in addition to ectopically located 
      junctional folds. Electrophysiological recordings revealed no change in quantal 
      content or MEPP frequency, but there was an increase in MEPP rise time in a 
      subset of endplates. No differences were observed in the rate or extent of 
      developmental synapse elimination. In vitro cleavage experiments revealed that 
      MMP3 directly cleaves agrin. Increased agrin immunofluorescence was observed at 
      the neuromuscular junctions of MMP3 null mutant mice. These results provide 
      strong evidence that MMP3 is involved in the control of synaptic structure at the 
      neuromuscular junction and they support the hypothesis that MMP3 is involved in 
      the regulation of agrin at the neuromuscular junction.
FAU - VanSaun, M
AU  - VanSaun M
AD  - Department of Anatomy and Cell Biology, University of Kansas Medical Center, 
      Kansas City, KS 66160, USA.
FAU - Herrera, A A
AU  - Herrera AA
FAU - Werle, M J
AU  - Werle MJ
LA  - eng
GR  - NS24805/NS/NINDS NIH HHS/United States
GR  - NS33320/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Neurocytol
JT  - Journal of neurocytology
JID - 0364620
RN  - 0 (Agrin)
RN  - 0 (Receptors, Cholinergic)
RN  - EC 3.4.24.17 (Matrix Metalloproteinase 3)
SB  - IM
MH  - Agrin/*metabolism
MH  - Animals
MH  - Cell Differentiation/genetics
MH  - Excitatory Postsynaptic Potentials/genetics
MH  - Fluorescent Antibody Technique
MH  - Matrix Metalloproteinase 3/*deficiency/genetics
MH  - Mice
MH  - Mice, Knockout
MH  - Microscopy, Electron
MH  - Neuromuscular Junction/*enzymology/*pathology/physiopathology
MH  - Reaction Time/genetics
MH  - Receptors, Cholinergic/metabolism
MH  - Synaptic Membranes/enzymology/*pathology/ultrastructure
MH  - Synaptic Transmission/*genetics
MH  - Up-Regulation/genetics
EDAT- 2004/03/27 05:00
MHDA- 2004/08/12 05:00
CRDT- 2004/03/27 05:00
PHST- 2004/03/27 05:00 [pubmed]
PHST- 2004/08/12 05:00 [medline]
PHST- 2004/03/27 05:00 [entrez]
AID - 5266238 [pii]
AID - 10.1023/B:NEUR.0000021907.68461.9c [doi]
PST - ppublish
SO  - J Neurocytol. 2003 Nov;32(9):1129-42. doi: 10.1023/B:NEUR.0000021907.68461.9c.