PMID- 10770843
OWN - NLM
STAT- MEDLINE
DCOM- 20000630
LR  - 20071114
IS  - 0022-3034 (Print)
IS  - 0022-3034 (Linking)
VI  - 43
IP  - 2
DP  - 2000 May
TI  - Matrix metalloproteinase-3 removes agrin from synaptic basal lamina.
PG  - 140-9
AB  - Agrin, a heparin sulfate proteoglycan, is an integral member of the synaptic 
      basal lamina and plays a critical role in the formation and maintenance of the 
      neuromuscular junction. The N-terminal region of agrin binds tightly to basal 
      lamina, while the C-terminal region interacts with a muscle-specific tyrosine 
      kinase (MuSK) to induce the formation of the postsynaptic apparatus. Although the 
      binding of agrin to basal lamina is tight, the binding of agrin to MuSK has yet 
      to be shown; therefore, basal lamina binding is critical for maintaining the 
      presentation of agrin to MuSK. Here we report evidence that supports our 
      hypothesis that matrix metalloproteinase-3 (MMP-3) is responsible for the removal 
      of agrin from synaptic basal lamina. Antibodies to the hinge region of human 
      MMP-3 recognize molecules concentrated at the frog neuromuscular junction in both 
      cross sections and whole mounts. Electron microscopy of neuromuscular junctions 
      stained with antibodies to MMP-3 reveals that staining is found in the 
      extracellular matrix surrounding the Schwann cell. Treatment of sections from 
      frog anterior tibialis muscle with MMP-3 results in a clear and reproducible 
      removal of agrin immunoreactivity from synaptic basal lamina. The same MMP-3 
      treatment does not alter anti-laminin staining. These results support our 
      hypothesis that synaptic activity results in the activation of MMP-3 at the 
      neuromuscular junction and that MMP-3 specifically removes agrin from synaptic 
      basal lamina.
CI  - Copyright 2000 John Wiley & Sons, Inc.
FAU - VanSaun, M
AU  - VanSaun M
AD  - Department of Anatomy and Cell Biology, The University of Kansas Medical Center, 
      Kansas City, Kansas 66160, USA.
FAU - Werle, M J
AU  - Werle MJ
LA  - eng
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 Neurobiol
JT  - Journal of neurobiology
JID - 0213640
RN  - 0 (Agrin)
RN  - 0 (Antibodies)
RN  - 0 (Bungarotoxins)
RN  - 0 (Laminin)
RN  - 0 (Rhodamines)
RN  - EC 3.4.24.17 (Matrix Metalloproteinase 3)
SB  - IM
EIN - J Neurobiol 2000 Sep 5;44(3):369
MH  - Agrin/*metabolism
MH  - Animals
MH  - Antibodies/metabolism
MH  - Antibody Specificity
MH  - Basement Membrane/drug effects/*metabolism/ultrastructure
MH  - Bungarotoxins/pharmacokinetics
MH  - Dose-Response Relationship, Drug
MH  - Immunohistochemistry
MH  - Laminin/metabolism
MH  - Male
MH  - Matrix Metalloproteinase 3/*metabolism/pharmacology
MH  - Microscopy, Electron
MH  - Muscle, Skeletal/drug effects/enzymology/innervation
MH  - Neuromuscular Junction/*metabolism/ultrastructure
MH  - Rana pipiens
MH  - Rhodamines
MH  - Synaptic Membranes/drug effects/*metabolism/ultrastructure
EDAT- 2000/04/19 09:00
MHDA- 2000/07/08 11:00
CRDT- 2000/04/19 09:00
PHST- 2000/04/19 09:00 [pubmed]
PHST- 2000/07/08 11:00 [medline]
PHST- 2000/04/19 09:00 [entrez]
AID - 10.1002/(SICI)1097-4695(200005)43:2<140::AID-NEU4>3.0.CO;2-K [pii]
PST - ppublish
SO  - J Neurobiol. 2000 May;43(2):140-9.