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PLoS Biol. 2018 Dec 26;16(12):e2006838. doi: 10.1371/journal.pbio.2006838. eCollection 2018 Dec.

An opposing function of paralogs in balancing developmental synapse maturation.

Author information

1
European Neuroscience Institute Göttingen, University Medical Center, Göttingen, Germany.
2
Collaborative Research Center 889, University of Göttingen, Göttingen, Germany.
3
Department of Neuroscience, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
4
Department of Systems Neuroscience, Universität Göttingen, Göttingen, Germany.
5
Department of Psychiatry and Psychotherapy, University Medical Center, Göttingen, Germany.
6
Department of Neuroanatomy, Medical School, Saarland University, Homburg, Germany.

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.

PMID:
30586380
PMCID:
PMC6324823
DOI:
10.1371/journal.pbio.2006838
[Indexed for MEDLINE]
Free PMC Article

Conflict of interest statement

The authors have declared that no competing interests exist.

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