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

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 o

SUBMITTER: Gonzalez-Calvo I 

PROVIDER: S-EPMC7972451 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature