Sushi domain-containing protein 4 controls synaptic plasticity and motor learning - Sorbonne Université
Journal Articles eLife Year : 2021

Sushi domain-containing protein 4 controls synaptic plasticity and motor learning

Martial Séveno
Oana Vigy
Yann Nadjar
Antoine Triller

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.

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Origin Publication funded by an institution

Dates and versions

hal-03160965 , version 2 (05-03-2021)
hal-03160965 , version 1 (16-11-2021)

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Inés Gonzalez-Calvo, Keerthana Iyer, Mélanie Carquin, Anouar Khayachi, Fernando A Giuliani, et al.. Sushi domain-containing protein 4 controls synaptic plasticity and motor learning. eLife, 2021, 10, ⟨10.7554/eLife.65712⟩. ⟨hal-03160965v2⟩
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