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Synaptic remodeling depends on signaling between serotonin receptors and the extracellular matrix

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Wlodarczyk J., Bijata M., Labus J., Guseva D., Michaluk P., Rusakov D. A., Dityatev A., Dzwonek J., Ponimaskin E.

Acta Neurobiologiae Experimentalis

2017

tom 77

nr Suppl.1

The rewiring of synaptic circuitry pertinent to memory formation in the brain has often been associated with morphological changes in dendritic spines and extracellular matrix (ECM) remodeling. Here, we linked these processes by uncovering the signaling pathway involving the serotonin 5-HT7 receptors (5 HT7R) the matrix metalloproteinase-9 (MMP-9), the hyaluronan receptor CD44, and the small GTPase Cdc42. We highlight a physical interaction between 5‑HT7R and CD44 (identified as a novel MMP 9 substrate in neurons) on the nanoscale, and find that 5-HT7R stimulation increases local MMP 9 activity triggering dendritic spines remodeling, synaptic pruning and impairment of long-term potentiation (LTP). The underlying molecular machinery involves 5-HT7R-mediated activation of MMP-9, which leads to CD44 cleavage followed by Cdc42 activation. Pharmacological/genetic suppression of this pathway rescues the 5-HT7R-induced synaptic changes and the deficit in LTP. Our results thus reveal causal interactions in a previously unknown molecular mechanism regulating neuronal plasticity. FINANCIAL SUPPORT: The work was supported by the National Science Centre (grant no. DEC-2012/06/M/ NZ3/00163), TANGO1/269352/NCBR/2015, Deutsche Forschungsgemeinschaft (grant no. PO732, excellence cluster REBIRTH), and ERA-NET Neuron/BMBF funding for the TargetECM project to E.P and A.D.

Ograniczanie wyników

1 Acta Neurobiologiae Experimentalis

1 Bijata M.

1 Dityatev A.

1 Dzwonek J.

1 Guseva D.

1 Labus J.

1 Michaluk P.

1 Ponimaskin E.

1 Rusakov D. A.

1 Wlodarczyk J.

1 2017

Wyniki wyszukiwania

Synaptic remodeling depends on signaling between serotonin receptors and the extracellular matrix