Journal Article

DZNE-2020-05611

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png 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.DZNE* ; Böhm, K.DZNE* ; Michaluk, P. ; Rusakov, D. A. ; Dityatev, A.DZNE* ; Wilczyński, G. ; Wlodarczyk, J. (Corresponding author) ; Ponimaskin, E.

2017
Elsevier [New York, NY]

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Please use a persistent id in citations: doi:10.1016/j.celrep.2017.05.023

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).

Keyword(s): Animals (MeSH) ; Cell Line, Tumor (MeSH) ; Dendritic Spines: drug effects (MeSH) ; Dendritic Spines: metabolism (MeSH) ; Extracellular Matrix: drug effects (MeSH) ; Extracellular Matrix: metabolism (MeSH) ; Hyaluronan Receptors: chemistry (MeSH) ; Hyaluronan Receptors: metabolism (MeSH) ; Long-Term Potentiation: drug effects (MeSH) ; Matrix Metalloproteinase 9: metabolism (MeSH) ; Mice (MeSH) ; Neurogenesis: drug effects (MeSH) ; Protein Binding: drug effects (MeSH) ; Protein Domains (MeSH) ; Receptors, Serotonin: metabolism (MeSH) ; Serotonin: analogs & derivatives (MeSH) ; Serotonin: pharmacology (MeSH) ; Signal Transduction: drug effects (MeSH) ; Synapses: drug effects (MeSH) ; Synapses: metabolism (MeSH) ; cdc42 GTP-Binding Protein: metabolism (MeSH) ; Hyaluronan Receptors ; Receptors, Serotonin ; serotonin 7 receptor ; Serotonin ; 5-carboxamidotryptamine ; Matrix Metalloproteinase 9 ; cdc42 GTP-Binding Protein

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Contributing Institute(s):

1. Molecular Neuroplasticity (AG Dityatev)

Research Program(s):

1. 342 - Disease Mechanisms and Model Systems (POF3-342) (POF3-342)

Appears in the scientific report 2017

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Database coverage:
; ; ; ; BIOSIS Previews ; Clarivate Analytics Master Journal List ; DOAJ Seal ; IF >= 5 ; JCR ; SCOPUS ; Web of Science Core Collection

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