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
Popis
Abstrakt: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.
ISSN:20734409
DOI:10.3390/cells9020260