Extracellular Metalloproteinases in the Plasticity of Excitatory and Inhibitory Synapses
Long-term synaptic plasticity is shaped by the controlled reorganization of the synaptic proteome. A key component of this process is local proteolysis performed by the family of extracellular matrix metalloproteinases (MMPs). In recent years, considerable progress was achieved in identifying extrac...
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| Format: | Article |
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MDPI AG
2021-08-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/10/8/2055 |
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| author | Grzegorz Wiera Jerzy W. Mozrzymas |
| author_facet | Grzegorz Wiera Jerzy W. Mozrzymas |
| author_sort | Grzegorz Wiera |
| collection | DOAJ |
| description | Long-term synaptic plasticity is shaped by the controlled reorganization of the synaptic proteome. A key component of this process is local proteolysis performed by the family of extracellular matrix metalloproteinases (MMPs). In recent years, considerable progress was achieved in identifying extracellular proteases involved in neuroplasticity phenomena and their protein substrates. Perisynaptic metalloproteinases regulate plastic changes at synapses through the processing of extracellular and membrane proteins. MMP9 was found to play a crucial role in excitatory synapses by controlling the NMDA-dependent LTP component. In addition, MMP3 regulates the L-type calcium channel-dependent form of LTP as well as the plasticity of neuronal excitability. Both MMP9 and MMP3 were implicated in memory and learning. Moreover, altered expression or mutations of different MMPs are associated with learning deficits and psychiatric disorders, including schizophrenia, addiction, or stress response. Contrary to excitatory drive, the investigation into the role of extracellular proteolysis in inhibitory synapses is only just beginning. Herein, we review the principal mechanisms of MMP involvement in the plasticity of excitatory transmission and the recently discovered role of proteolysis in inhibitory synapses. We discuss how different matrix metalloproteinases shape dynamics and turnover of synaptic adhesome and signal transduction pathways in neurons. Finally, we discuss future challenges in exploring synapse- and plasticity-specific functions of different metalloproteinases. |
| first_indexed | 2024-03-10T08:55:19Z |
| format | Article |
| id | doaj.art-2e050316e8554b8fa292d719b8f78664 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T08:55:19Z |
| publishDate | 2021-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-2e050316e8554b8fa292d719b8f786642023-11-22T07:11:05ZengMDPI AGCells2073-44092021-08-01108205510.3390/cells10082055Extracellular Metalloproteinases in the Plasticity of Excitatory and Inhibitory SynapsesGrzegorz Wiera0Jerzy W. Mozrzymas1Department of Biophysics and Neuroscience, Wroclaw Medical University, 50-368 Wroclaw, PolandDepartment of Biophysics and Neuroscience, Wroclaw Medical University, 50-368 Wroclaw, PolandLong-term synaptic plasticity is shaped by the controlled reorganization of the synaptic proteome. A key component of this process is local proteolysis performed by the family of extracellular matrix metalloproteinases (MMPs). In recent years, considerable progress was achieved in identifying extracellular proteases involved in neuroplasticity phenomena and their protein substrates. Perisynaptic metalloproteinases regulate plastic changes at synapses through the processing of extracellular and membrane proteins. MMP9 was found to play a crucial role in excitatory synapses by controlling the NMDA-dependent LTP component. In addition, MMP3 regulates the L-type calcium channel-dependent form of LTP as well as the plasticity of neuronal excitability. Both MMP9 and MMP3 were implicated in memory and learning. Moreover, altered expression or mutations of different MMPs are associated with learning deficits and psychiatric disorders, including schizophrenia, addiction, or stress response. Contrary to excitatory drive, the investigation into the role of extracellular proteolysis in inhibitory synapses is only just beginning. Herein, we review the principal mechanisms of MMP involvement in the plasticity of excitatory transmission and the recently discovered role of proteolysis in inhibitory synapses. We discuss how different matrix metalloproteinases shape dynamics and turnover of synaptic adhesome and signal transduction pathways in neurons. Finally, we discuss future challenges in exploring synapse- and plasticity-specific functions of different metalloproteinases.https://www.mdpi.com/2073-4409/10/8/2055metalloproteinaseproteolysissynaptic plasticityGABAinhibitory synapseLTP |
| spellingShingle | Grzegorz Wiera Jerzy W. Mozrzymas Extracellular Metalloproteinases in the Plasticity of Excitatory and Inhibitory Synapses Cells metalloproteinase proteolysis synaptic plasticity GABA inhibitory synapse LTP |
| title | Extracellular Metalloproteinases in the Plasticity of Excitatory and Inhibitory Synapses |
| title_full | Extracellular Metalloproteinases in the Plasticity of Excitatory and Inhibitory Synapses |
| title_fullStr | Extracellular Metalloproteinases in the Plasticity of Excitatory and Inhibitory Synapses |
| title_full_unstemmed | Extracellular Metalloproteinases in the Plasticity of Excitatory and Inhibitory Synapses |
| title_short | Extracellular Metalloproteinases in the Plasticity of Excitatory and Inhibitory Synapses |
| title_sort | extracellular metalloproteinases in the plasticity of excitatory and inhibitory synapses |
| topic | metalloproteinase proteolysis synaptic plasticity GABA inhibitory synapse LTP |
| url | https://www.mdpi.com/2073-4409/10/8/2055 |
| work_keys_str_mv | AT grzegorzwiera extracellularmetalloproteinasesintheplasticityofexcitatoryandinhibitorysynapses AT jerzywmozrzymas extracellularmetalloproteinasesintheplasticityofexcitatoryandinhibitorysynapses |