Cleavage of neuronal synaptosomal-associated protein of 25 kDa by exogenous matrix metalloproteinase-7
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Updated: Jul 15, 2026
Preparation of Synaptic Plasma Membrane and Postsynaptic Density Proteins Using a Discontinuous Sucrose Gradient
Published on: September 3, 2014
Arek Szklarczyk1, George Oyler, Ron McKay
1Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA. aszklar1@jhmi.edu
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.
Insights
Matrix metalloproteinase-7 (MMP-7) cleaves the intraneuronal protein SNAP-25, impacting neurotransmitter release. This finding suggests potential implications for brain inflammation and neuronal function.
Area of Science:
- Neuroscience
- Molecular Biology
- Enzymology
Background:
- Matrix metalloproteinases (MMPs) are zinc-dependent enzymes primarily known for roles in cancer and inflammation.
- MMPs typically degrade extracellular matrix proteins.
Purpose of the Study:
- To investigate the potential for MMP-7 to cleave intracellular neuronal proteins.
- To identify the specific neuronal substrate and cleavage site for MMP-7.
Main Methods:
- Western blot analysis of cultured neurons using an N-terminal specific antibody for SNAP-25.
- Biochemical assays with recombinant SNAP-25.
- Inhibition studies using chlorpromazine and phenylarsine oxide.
Main Results:
- MMP-7 cleaves synaptosomal-associated protein of 25 kDa (SNAP-25), an intraneuronal protein critical for vesicular fusion.
- Cleavage occurs at amino acid 129 of SNAP-25.
- Endocytosis inhibitors partially block MMP-7's ability to cleave SNAP-25.
Conclusions:
- Exogenous MMP-7 can access and cleave intracellular substrates like SNAP-25.
- MMP-7-mediated cleavage of SNAP-25 may impair neurotransmitter release.
- Further research is needed to explore SNAP-25 function during brain inflammation.
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