Cleavage of Neuronal Synaptosomal-associated Protein of 25 Kda by Exogenous Matrix Metalloproteinase-7.
From: Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA. aszklar1@jhmi.edu
Journal of neurochemistry
- Publish Date: Aug 2007
- ISSN: 0022-3042
- Volume: 102
- Issue: 4
- Pages: 1256-63
- Medium: Print
- Language: English
- Citation (JAMA): Szklarczyk Arek, Oyler George, McKay Ron, et al. Cleavage of Neuronal Synaptosomal-associated Protein of 25 Kda by Exogenous Matrix Metalloproteinase-7.. J. Neurochem. Aug 2007;102:1256-63
Abstract
Matrix metalloproteinases (MMPs) belong to a family of zinc dependent enzymes best studied for their role in cancer and inflammation. Though MMPs typically target extracellular proteins, here we show that MMP-7, an MMP family member which lacks a C-terminal hemopexin-like domain, can cleave an intraneuronal protein that is critical to vesicular fusion and neurotransmitter release, synaptosomal-associated protein of 25 kDa (SNAP-25). Western blot analysis using an N-terminal specific antibody on extracts from cultured neurons suggests that cleavage occurs towards the C-terminal portion of SNAP 25. Additional studies with recombinant SNAP-25 demonstrate that cleavage occurs at amino acid 129. The ability of MMP-7 to cleave SNAP-25 is diminished by chlorpromazine and phenylarsine oxide, inhibitors of clathrin dependent endocytosis. Together, these results imply that exogenous MMP-7 can access an intraneuronal substrate and suggest that additional studies may be warranted to determine if SNAP function is impaired with brain inflammation.
Mesh Headings (Keywords): Animals, Cells, Cultured, Cerebral Cortex, Clathrin, Embryo, Mammalian, Endocytosis, Humans, Matrix Metalloproteinase 7, Neurons, Rats, Synaptosomal-Associated Protein 25, Time Factors
Check for Full Text / PubMed Unique Identifier (PMID): 17472697
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