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.
Original language | English (US) |
---|---|
Pages (from-to) | 1256-1263 |
Number of pages | 8 |
Journal | Journal of Neurochemistry |
Volume | 102 |
Issue number | 4 |
DOIs | |
State | Published - Aug 2007 |
Keywords
- Endocytosis
- Matrilysin
- Matrix metalloproteinase-7
- Neuron
- Synaptosomal-associated protein of 25 kDa
ASJC Scopus subject areas
- Biochemistry
- Cellular and Molecular Neuroscience