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Synaptic Remodeling Depends on Signaling between Serotonin Receptors and the Extracellular Matrix

Bijata, M; Labus, J; Guseva, D; Stawarski, M; Butzlaff, M; Dzwonek, J; Schneeberg, J; ... Ponimaskin, E; + view all (2017) Synaptic Remodeling Depends on Signaling between Serotonin Receptors and the Extracellular Matrix. Cell Reports , 19 (9) pp. 1767-1782. 10.1016/j.celrep.2017.05.023. Green open access

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Abstract

Rewiring of synaptic circuitry pertinent to memory formation has been associated with morphological changes in dendritic spines and with extracellular matrix (ECM) remodeling. Here, we mechanistically link these processes by uncovering a signaling pathway involving the serotonin 5-HT7 receptor (5-HT7R), 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 an MMP-9 substrate in neurons) and find that 5-HT7R stimulation increases local MMP-9 activity, triggering dendritic spine 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. One important physiological consequence of this interaction includes an increase in neuronal outgrowth and elongation of dendritic spines, which might have a positive effect on complex neuronal processes (e.g., reversal learning and neuronal regeneration).

Type: Article
Title: Synaptic Remodeling Depends on Signaling between Serotonin Receptors and the Extracellular Matrix
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.celrep.2017.05.023
Publisher version: http://doi.org/10.1016/j.celrep.2017.05.023
Language: English
Additional information: © 2017 The Authors. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Keywords: Science & Technology, Life Sciences & Biomedicine, Cell Biology, LONG-TERM POTENTIATION, SERUM RESPONSE FACTOR, 5-HT7 RECEPTOR, NEURONAL MORPHOLOGY, CD44 CLEAVAGE, MATRIX-METALLOPROTEINASE-9, PLASTICITY, MMP-9, ACTIVATION, OLIGOMERIZATION, dendritic spines; synaptic plasticity; proteolysis; extracellular matrix; MMP-9; CD44; 5-HT7R; Cdc42
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Clinical and Experimental Epilepsy
URI: https://discovery.ucl.ac.uk/id/eprint/1558689
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