Dopamine Receptor Activation Modulates the Integrity of the Perisynaptic Extracellular Matrix at Excitatory Synapses
| Autor: | Christine E Gee, Jessica Mitlöhner, Alexander Dityatev, Hartmut Niekisch, Renato Frischknecht, Max F. K. Happel, Constanze I. Seidenbecher, Rahul Kaushik, Eckart D. Gundelfinger, Armand Blondiaux |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Male metabolism [Brevican] metabolism [Furin] chondroitin sulfate proteoglycan Calcium in biology Receptors Dopamine 0302 clinical medicine ADAMTS Proteins Homer Scaffolding Proteins Perisynaptic extracellular matrix Cyclic AMP Brevican lcsh:QH301-705.5 Cells Cultured Furin ADAMTS 4/5 Chemistry ADAMTS brevican General Medicine Cell biology Extracellular Matrix Dopamine receptor metabolism [Presynaptic Terminals] Excitatory postsynaptic potential NMDA receptor D1/D5 receptors NMDA receptors Ion Channel Gating metabolism [Cyclic AMP] metabolism [Extracellular Matrix] Calcium Channels L-Type metabolism [Homer Scaffolding Proteins] metabolism [Prefrontal Cortex] Presynaptic Terminals Prefrontal Cortex metabolism [Cyclic AMP-Dependent Protein Kinases] Receptors N-Methyl-D-Aspartate Article 03 medical and health sciences ddc:570 Extracellular Animals Rats Wistar metabolism [Receptors N-Methyl-D-Aspartate] metabolism [ADAMTS Proteins] metabolism [Calcium-Calmodulin-Dependent Protein Kinase Type 2] metabolism [Synapses] metabolism [Calcium Channels L-Type] metabolism [Receptors Dopamine] Cyclic AMP-Dependent Protein Kinases 030104 developmental biology lcsh:Biology (General) Synapses Calcium-Calmodulin-Dependent Protein Kinase Type 2 030217 neurology & neurosurgery |
| Zdroj: | Cells Cells 9(2), 260 (2020). doi:10.3390/cells9020260 Cells, 9(2):260 Cells, Vol 9, Iss 2, p 260 (2020) Volume 9 Issue 2 |
| ISSN: | 2073-4409 |
| DOI: | 10.3390/cells9020260 |
| Popis: | In the brain, Hebbian-type and homeostatic forms of plasticity are affected by neuromodulators like dopamine (DA). Modifications of the perisynaptic extracellular matrix (ECM), which control the functions and mobility of synaptic receptors as well as the diffusion of transmitters and neuromodulators in the extracellular space, are crucial for the manifestation of plasticity. Mechanistic links between synaptic activation and ECM modifications are largely unknown. Here, we report that neuromodulation via D1-type DA receptors can induce targeted ECM proteolysis specifically at excitatory synapses of rat cortical neurons via proteases ADAMTS-4 and -5. We showed that receptor activation induces increased proteolysis of brevican (BC) and aggrecan, two major constituents of the adult ECM both in vivo and in vitro. ADAMTS immunoreactivity was detected near synapses, and shRNA-mediated knockdown reduced BC cleavage. We have outlined a molecular scenario of how synaptic activity and neuromodulation are linked to ECM rearrangements via increased cAMP levels, NMDA receptor activation, and intracellular calcium signaling. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|