RGD Reference Report - Axotomy of sympathetic neurons activates the metalloproteinase-2 enzymatic pathway. - Rat Genome Database
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Axotomy of sympathetic neurons activates the metalloproteinase-2 enzymatic pathway.

Authors: Leone, L  De Stefano, ME  Del Signore, A  Petrucci, TC  Paggi, P 
Citation: Leone L, etal., J Neuropathol Exp Neurol. 2005 Nov;64(11):1007-17.
RGD ID: 11541065
Pubmed: (View Article at PubMed) PMID:16254495

We have previously shown that intraganglionic synapse disassembly consequent on superior cervical ganglion (SCG) neuron axotomy was preceded by the loss of the dystroglycan beta subunit (beta-DG) localized at the postsynaptic specializations. Because DG, a transmembrane molecular complex bridging the extracellular matrix to the cortical cytoskeleton, could be a physiological target of metalloproteinases (MMPs) 2 and 9, we investigated their possible involvement in the injury-induced intraganglionic synapse disassembly. In rat SCG, only MMP-2 was present and localized in both neurons and nonneuronal cells. After ganglion neuron axotomy, both MMP-2 activity and protein level increased, whereas the level of its mRNA was unchanged, suggesting prominent MMP-2 posttranslational regulation. mRNA and protein levels of the enzymes involved in the MMP-2 activation pathway, the membrane-type 1-MMP (MT1-MMP), and the tissue inhibitor of metalloproteinase-2 (TIMP-2) also increased after injury with a time course that correlated with that of MMP-2 activation. In addition, postganglionic nerve crush induced an increase in the beta-DG 30-kDa fragment produced by the MMP-dependent degradation of DG. These data suggest that MMP-2 activated during SCG neuron reaction to axotomy may degrade postsynaptic DG, contributing to the disruption of the molecular bridge between pre- and postsynaptic elements and disassembly of the intraganglionic synapses.


Disease Annotations    

Objects Annotated

Genes (Rattus norvegicus)
Dag1  (dystroglycan 1)

Genes (Mus musculus)
Dag1  (dystroglycan 1)

Genes (Homo sapiens)
DAG1  (dystroglycan 1)

Additional Information