Sushi domain-containing protein 4 controls synaptic plasticity and motor learning
- Collège de France, France
- CNRS, France
- Sorbonne University, France
- École Normale Supérieure, France
- University of Lyon - INSERM - CNRS, France
- Université Pierre et Marie Curie (UPMC), France
Abstract
Fine control of protein stoichiometry at synapses underlies brain function and plasticity. How proteostasis is controlled independently for each type of synaptic protein in a synapse-specific and activity-dependent manner remains unclear. Here we show that Susd4, a gene coding for a complement-related transmembrane protein, is expressed by many neuronal populations starting at the time of synapse formation. Constitutive loss-of-function of Susd4 in the mouse impairs motor coordination adaptation and learning, prevents long-term depression at cerebellar synapses, and leads to misregulation of activity-dependent AMPA receptor subunit GluA2 degradation. We identified several proteins with known roles in the regulation of AMPA receptor turnover, in particular ubiquitin ligases of the NEDD4 subfamily, as SUSD4 binding partners. Our findings shed light on the potential role of SUSD4 mutations in neurodevelopmental diseases.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting files.
Article and author information
Author details
JeanLouis Bessereau
Funding
ATIP-AVENIR (RSE11005JSA)
- Fekrije Selimi
Labex MEMOLIFE (ANR-10-LABX-54 MEMO LIFE)
- Keerthana Iyer
Ecole des Neurosciences de Paris
- Keerthana Iyer
Labex BIOPSY (ANR-11-IDEX-0004-02)
- Laure Rondi-Reig
Idex PSL (ANR-10-IDEX-0001-02 PSL*)
- Fekrije Selimi
Agence Nationale de la Recherche (ANR 9139SAMA90010901)
- Fekrije Selimi
Agence Nationale de la Recherche (ANR 9139SAMA90010901)
- Philippe Isope
Agence Nationale de la Recherche (ANR-15-CE37-0001-01 CeMod)
- Fekrije Selimi
Agence Nationale de la Recherche (ANR-15-CE37-0001-01 CeMod)
- Philippe Isope
Fondation pour la Recherche Médicale (DEQ20150331748)
- Fekrije Selimi
Fondation pour la Recherche Médicale (DEQ20140329514)
- Philippe Isope
H2020 European Research Council (SynID 724601)
- Fekrije Selimi
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: All animal protocols were approved by the Comité Regional d'Ethique en Experimentation Animale (no. 00057.01) and animals were housed in authorized facilities of the CIRB (# C75 05 12).
Reviewing Editor
- Megan R Carey, Champalimaud Foundation, Portugal
Version history
- Received: December 13, 2020
- Accepted: March 3, 2021
- Accepted Manuscript published: March 4, 2021 (version 1)
- Version of Record published: March 18, 2021 (version 2)
Copyright
© 2021, Gonzalez-Calvo et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Sushi domain-containing protein 4 controls synaptic plasticity and motor learning
eLife 10:e65712.
https://doi.org/10.7554/eLife.65712
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