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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- 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