title: Cleavage of neuronal synaptosomal-associated protein of 25 kDa by exogenous matrix metalloproteinase-7.
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.
authors.affiliation: Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA. aszklar1@jhmi.edu
authors.forename: Arek
authors.initials: A
authors.lastname: Szklarczyk
authors.forename: George
authors.initials: G
authors.lastname: Oyler
authors.forename: Ron
authors.initials: R
authors.lastname: McKay
authors.forename: Charles
authors.initials: C
authors.lastname: Gerfen
authors.forename: Katherine
authors.initials: K
authors.lastname: Conant
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D002966:Clathrin / Q000378:metabolism; D004622:Embryo, Mammalian; D004705:Endocytosis / Q000187:drug effects; D006801:Humans; D020783:Matrix Metalloproteinase 7 / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects*; D051381:Rats; D050825:Synaptosomal-Associated Protein 25 / Q000378:metabolism*; D013997:Time Factors
chemical_list: D002966:Clathrin; D050825:Synaptosomal-Associated Protein 25; D020783:Matrix Metalloproteinase 7