Axotomy of sympathetic neurons activates the metalloproteinase-2 enzymatic pathway.
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.[1]References
- Axotomy of sympathetic neurons activates the metalloproteinase-2 enzymatic pathway. Leone, L., De Stefano, M.E., Del Signore, A., Petrucci, T.C., Paggi, P. J. Neuropathol. Exp. Neurol. (2005) [Pubmed]
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