An opposing function of paralogs in balancing developmental synapse maturation

2018 | journal article. A publication with affiliation to the University of Göttingen.

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​Favaro PD, Huang X, Hosang L, Stodieck S, Cui L, Liu, Yu-Zhang, et al. ​An opposing function of paralogs in balancing developmental synapse maturation​. ​​PLOS Biology. ​2018;​16​(12). ​doi:10.1371/journal.pbio.2006838. 

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Authors
Favaro, Plinio D.; Huang, Xiaojie; Hosang, Leon; Stodieck, Sophia; Cui, Lei; Liu, Yu-Zhang; Engelhardt, Karl-Alexander; Schmitz, Frank; Dong, Yan; Löwel, Siegrid; Schlüter, Oliver M. 
Abstract
The disc-large (DLG)-membrane-associated guanylate kinase (MAGUK) family of proteins forms a central signaling hub of the glutamate receptor complex. Among this family, some proteins regulate developmental maturation of glutamatergic synapses, a process vulnerable to aberrations, which may lead to neurodevelopmental disorders. As is typical for paralogs, the DLG-MAGUK proteins postsynaptic density (PSD)-95 and PSD-93 share similar functional domains and were previously thought to regulate glutamatergic synapses similarly. Here, we show that they play opposing roles in glutamatergic synapse maturation. Specifically, PSD-95 promoted, whereas PSD-93 inhibited maturation of immature α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid-type glutamate receptor (AMPAR)-silent synapses in mouse cortex during development. Furthermore, through experience-dependent regulation of its protein levels, PSD-93 directly inhibited PSD-95's promoting effect on silent synapse maturation in the visual cortex. The concerted function of these two paralogs governed the critical period of juvenile ocular dominance plasticity (jODP), and fine-tuned visual perception during development. In contrast to the silent synapse-based mechanism of adjusting visual perception, visual acuity improved by different mechanisms. Thus, by controlling the pace of silent synapse maturation, the opposing but properly balanced actions of PSD-93 and PSD-95 are essential for fine-tuning cortical networks for receptive field integration during developmental critical periods, and imply aberrations in either direction of this process as potential causes for neurodevelopmental disorders.
Issue Date
2018
Journal
PLOS Biology 
Project
SFB 889: Zelluläre Mechanismen sensorischer Verarbeitung 
Organization
European Neuroscience Institute Göttingen ; Abteilung Systemische Neurobiologie ; Klinik für Psychiatrie und Psychotherapie 
ISSN
1545-7885
Language
English
Sponsor
Open-Access-Publikationsfonds 2018

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