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Cleavage of neuronal synaptosomal‐associated protein of 25 kDa by exogenous matrix metalloproteinase‐7
Author(s) -
Szklarczyk Arek,
Oyler George,
McKay Ron,
Gerfen Charles,
Conant Katherine
Publication year - 2007
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2007.04625.x
Subject(s) - matrix metalloproteinase , endocytosis , metalloproteinase , syntaxin , proteolysis , biochemistry , chemistry , microbiology and biotechnology , western blot , cleavage (geology) , matrilysin , cleave , snap , phenylarsine oxide , biology , exocytosis , enzyme , receptor , gene , fracture (geology) , computer graphics (images) , computer science , paleontology , secretion
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.