Sushi domain-containing protein 4 controls synaptic plasticity and motor learning
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-rela...
| Main Authors: | , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
eLife Sciences Publications Ltd
2021-03-01
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| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/65712 |
| _version_ | 1818019913981231104 |
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| author | Inés González-Calvo Keerthana Iyer Mélanie Carquin Anouar Khayachi Fernando A Giuliani Séverine M Sigoillot Jean Vincent Martial Séveno Maxime Veleanu Sylvana Tahraoui Mélanie Albert Oana Vigy Célia Bosso-Lefèvre Yann Nadjar Andréa Dumoulin Antoine Triller Jean-Louis Bessereau Laure Rondi-Reig Philippe Isope Fekrije Selimi |
| author_facet | Inés González-Calvo Keerthana Iyer Mélanie Carquin Anouar Khayachi Fernando A Giuliani Séverine M Sigoillot Jean Vincent Martial Séveno Maxime Veleanu Sylvana Tahraoui Mélanie Albert Oana Vigy Célia Bosso-Lefèvre Yann Nadjar Andréa Dumoulin Antoine Triller Jean-Louis Bessereau Laure Rondi-Reig Philippe Isope Fekrije Selimi |
| author_sort | Inés González-Calvo |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-14T07:58:09Z |
| format | Article |
| id | doaj.art-01bd3175794d47878ad8b245d0150a1d |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-14T07:58:09Z |
| publishDate | 2021-03-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-01bd3175794d47878ad8b245d0150a1d2022-12-22T02:04:58ZengeLife Sciences Publications LtdeLife2050-084X2021-03-011010.7554/eLife.65712Sushi domain-containing protein 4 controls synaptic plasticity and motor learningInés González-Calvo0https://orcid.org/0000-0002-2652-2160Keerthana Iyer1https://orcid.org/0000-0002-4384-6781Mélanie Carquin2Anouar Khayachi3Fernando A Giuliani4Séverine M Sigoillot5Jean Vincent6Martial Séveno7Maxime Veleanu8Sylvana Tahraoui9Mélanie Albert10Oana Vigy11Célia Bosso-Lefèvre12Yann Nadjar13Andréa Dumoulin14Antoine Triller15Jean-Louis Bessereau16https://orcid.org/0000-0002-3088-7621Laure Rondi-Reig17https://orcid.org/0000-0003-1006-0501Philippe Isope18https://orcid.org/0000-0002-0630-5935Fekrije Selimi19https://orcid.org/0000-0001-7704-5897Center for Interdisciplinary Research in Biology (CIRB), Collège de France, CNRS, INSERM, PSL Research University, Paris, France; Institut des Neurosciences Cellulaires et Intégratives (INCI), CNRS, Université de Strasbourg, Strasbourg, FranceCenter for Interdisciplinary Research in Biology (CIRB), Collège de France, CNRS, INSERM, PSL Research University, Paris, FranceCenter for Interdisciplinary Research in Biology (CIRB), Collège de France, CNRS, INSERM, PSL Research University, Paris, FranceCenter for Interdisciplinary Research in Biology (CIRB), Collège de France, CNRS, INSERM, PSL Research University, Paris, FranceInstitut des Neurosciences Cellulaires et Intégratives (INCI), CNRS, Université de Strasbourg, Strasbourg, FranceCenter for Interdisciplinary Research in Biology (CIRB), Collège de France, CNRS, INSERM, PSL Research University, Paris, FranceInstitut Biology Paris Seine (IBPS), Neuroscience Paris Seine (NPS), CeZaMe, CNRS, Sorbonne University, INSERM, Paris, FranceBioCampus Montpellier, CNRS, INSERM, Université de Montpellier, Montpellier, FranceCenter for Interdisciplinary Research in Biology (CIRB), Collège de France, CNRS, INSERM, PSL Research University, Paris, FranceCenter for Interdisciplinary Research in Biology (CIRB), Collège de France, CNRS, INSERM, PSL Research University, Paris, FranceCenter for Interdisciplinary Research in Biology (CIRB), Collège de France, CNRS, INSERM, PSL Research University, Paris, FranceInstitut de Génomique Fonctionnelle, CNRS, INSERM, Université de Montpellier, Montpellier, FranceCenter for Interdisciplinary Research in Biology (CIRB), Collège de France, CNRS, INSERM, PSL Research University, Paris, FranceÉcole Normale Supérieure, Institut de Biologie de l'ENS, INSERM, CNRS, PSL Research University, Paris, FranceÉcole Normale Supérieure, Institut de Biologie de l'ENS, INSERM, CNRS, PSL Research University, Paris, FranceÉcole Normale Supérieure, Institut de Biologie de l'ENS, INSERM, CNRS, PSL Research University, Paris, FranceUniversité de Lyon, Université Claude Bernard Lyon 1, CNRS UMR 5310, INSERM U 1217, Institut Neuromyogène, Lyon, FranceInstitut Biology Paris Seine (IBPS), Neuroscience Paris Seine (NPS), CeZaMe, CNRS, Sorbonne University, INSERM, Paris, FranceInstitut des Neurosciences Cellulaires et Intégratives (INCI), CNRS, Université de Strasbourg, Strasbourg, FranceCenter for Interdisciplinary Research in Biology (CIRB), Collège de France, CNRS, INSERM, PSL Research University, Paris, FranceFine 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.https://elifesciences.org/articles/65712synapseplasticitycerebellumproteostasis |
| spellingShingle | Inés González-Calvo Keerthana Iyer Mélanie Carquin Anouar Khayachi Fernando A Giuliani Séverine M Sigoillot Jean Vincent Martial Séveno Maxime Veleanu Sylvana Tahraoui Mélanie Albert Oana Vigy Célia Bosso-Lefèvre Yann Nadjar Andréa Dumoulin Antoine Triller Jean-Louis Bessereau Laure Rondi-Reig Philippe Isope Fekrije Selimi Sushi domain-containing protein 4 controls synaptic plasticity and motor learning eLife synapse plasticity cerebellum proteostasis |
| title | Sushi domain-containing protein 4 controls synaptic plasticity and motor learning |
| title_full | Sushi domain-containing protein 4 controls synaptic plasticity and motor learning |
| title_fullStr | Sushi domain-containing protein 4 controls synaptic plasticity and motor learning |
| title_full_unstemmed | Sushi domain-containing protein 4 controls synaptic plasticity and motor learning |
| title_short | Sushi domain-containing protein 4 controls synaptic plasticity and motor learning |
| title_sort | sushi domain containing protein 4 controls synaptic plasticity and motor learning |
| topic | synapse plasticity cerebellum proteostasis |
| url | https://elifesciences.org/articles/65712 |
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