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.
Leone
Lucia
L
Dipartimento di Biologia Cellulare e dello Sviluppo, Università La Sapienza, Roma, Italy.
De Stefano
M Egle
ME
Del Signore
Arianna
A
Petrucci
Tamara C
TC
Paggi
Paola
P
D000818:Animals; D015153:Blotting, Western; D005786:Gene Expression Regulation / Q000502:physiology*; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D008854:Microscopy, Electron / Q000379:methods; D009409:Nerve Crush / Q000379:methods; D009474:Neurons / Q000201:enzymology* / Q000648:ultrastructure; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013347:Subcellular Fractions / Q000378:metabolism / Q000648:ultrastructure; D017783:Superior Cervical Ganglion / Q000166:cytology*; D013562:Sympathectomy; D013997:Time Factors
D012333:RNA, Messenger; D020778:Matrix Metalloproteinase 2