PMID- 17525979 OWN - NLM STAT- MEDLINE DCOM- 20071120 LR - 20070820 IS - 1932-8451 (Print) IS - 1932-8451 (Linking) VI - 67 IP - 11 DP - 2007 Sep 15 TI - Activation of Matrix Metalloproteinase-3 is altered at the frog neuromuscular junction following changes in synaptic activity. PG - 1488-97 AB - The extracellular matrix surrounding the neuromuscular junction is a highly specialized and dynamic structure. Matrix Metalloproteinases are enzymes that sculpt the extracellular matrix. Since synaptic activity is critical to the structure and function of this synapse, we investigated whether changes in synaptic activity levels could alter the activity of Matrix Metalloproteinases at the neuromuscular junction. In particular, we focused on Matrix Metalloproteinase 3 (MMP3), since antibodies to MMP3 recognize molecules at the frog neuromuscular junction, and MMP3 cleaves a number of synaptic basal lamina molecules, including agrin. Here we show that the fluorogenic compound (M2300) can be used to perform in vivo proteolytic imaging of the frog neuromuscular junction to directly measure the activity state of MMP3. Application of this compound reveals that active MMP3 is concentrated at the normal frog neuromuscular junction, and is tightly associated with the terminal Schwann cell. Blocking presynaptic activity via denervation, or TTX nerve blockade, results in a decreased level of active MMP3 at the neuromuscular junction. The loss of active MMP3 at the neuromuscular junction in denervated muscles can result from decreased activation of pro-MMP3, or it could result from increased inhibition of MMP3. These results support the hypothesis that changes in synaptic activity can alter the level of active MMP3 at the neuromuscular junction. CI - (c) 2007 Wiley Periodicals, Inc. FAU - VanSaun, M AU - VanSaun M AD - Department of Anatomy and Cell Biology, University of Kansas Medical Center, Kansas City, KS 66160, USA. FAU - Humburg, B C AU - Humburg BC FAU - Arnett, M G AU - Arnett MG FAU - Pence, M AU - Pence M FAU - Werle, M J AU - Werle MJ LA - eng GR - NS33320/NS/NINDS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PL - United States TA - Dev Neurobiol JT - Developmental neurobiology JID - 101300215 RN - 0 (Fluorescent Dyes) RN - 0 (Sodium Channel Blockers) RN - 4368-28-9 (Tetrodotoxin) RN - EC 3.4.24.17 (Matrix Metalloproteinase 3) SB - IM MH - Animals MH - Enzyme Activation/physiology MH - Extracellular Matrix/*metabolism MH - Fluorescent Dyes MH - Matrix Metalloproteinase 3/*metabolism MH - Neuromuscular Junction/cytology/drug effects/*enzymology MH - Neuronal Plasticity/physiology MH - Rana pipiens/anatomy & histology/*physiology MH - Schwann Cells/enzymology MH - Sodium Channel Blockers/pharmacology MH - Staining and Labeling/methods MH - Synaptic Transmission/drug effects/*physiology MH - Tetrodotoxin/pharmacology EDAT- 2007/05/26 09:00 MHDA- 2007/12/06 09:00 CRDT- 2007/05/26 09:00 PHST- 2007/05/26 09:00 [pubmed] PHST- 2007/12/06 09:00 [medline] PHST- 2007/05/26 09:00 [entrez] AID - 10.1002/dneu.20523 [doi] PST - ppublish SO - Dev Neurobiol. 2007 Sep 15;67(11):1488-97. doi: 10.1002/dneu.20523.