| Autor: |
Philippe Isope, Oana Vigy, Célia Bosso-Lefèvre, Andréa Dumoulin, Mélanie Albert, Fernando A Giuliani, Jean-Louis Bessereau, Inés González-Calvo, Sylvana Tahraoui, Séverine M. Sigoillot, Anouar Khayachi, Maxime Veleanu, Mélanie Carquin, Keerthana Iyer, Yann Nadjar, Martial Séveno, Laure Rondi-Reig, Antoine Triller, Fekrije Selimi, Jean Vincent |
| Rok vydání: |
2019 |
| Předmět: |
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| Zdroj: |
bioRxiv |
| DOI: |
10.1101/859587 |
| Popis: |
SummaryAt excitatory synapses, the choice between recycling or degradation of glutamate AMPA receptors controls the direction of synaptic plasticity. In this context, how the degradation machinery is targeted to specific synaptic substrates in an activity-dependent manner is not understood. Here we show that SUSD4, a complement-related transmembrane protein, is a tether for HECT ubiquitin ligases of the NEDD4 subfamily, which promote the degradation of a large number of cellular substrates. SUSD4 is expressed by many neuronal populations starting at the time of synapse formation. Loss-of-function ofSusd4in the mouse prevents activity-dependent degradation of the GLUA2 AMPA receptor subunit and long-term depression at cerebellar synapses, and leads to impairment in motor coordination adaptation and learning. SUSD4 could thus act as an adaptor targeting NEDD4 ubiquitin ligases to AMPA receptors during long-term synaptic plasticity. These findings shed light on the potential contribution ofSUSD4mutations to the etiology of neurodevelopmental diseases. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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