RT Journal Article
SR Electronic
T1 SUSD4 controls GLUA2 degradation, synaptic plasticity and motor learning
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 859587
DO 10.1101/859587
A1 I. González-Calvo
A1 K. Iyer
A1 M. Carquin
A1 A. Khayachi
A1 F.A. Giuliani
A1 J. Vincent
A1 M. Séveno
A1 S.M. Sigoillot
A1 M. Veleanu
A1 S. Tahraoui
A1 M. Albert
A1 O. Vigy
A1 C. Bosso-Lefèvre
A1 Y. Nadjar
A1 A. Dumoulin
A1 A. Triller
A1 J.-L. Bessereau
A1 L. Rondi-Reig
A1 P. Isope
A1 F. Selimi
YR 2020
UL http://biorxiv.org/content/early/2020/12/16/859587.abstract
AB 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 complement-related transmembrane protein, binds the AMPA receptor subunit GLUA2 and controls its activity-dependent degradation. Several proteins with known roles in the regulation of AMPA receptor turnover, in particular ubiquitin ligases of the NEDD4 subfamily, are identified as SUSD4 binding partners. SUSD4 is expressed by many neuronal populations starting at the time of synapse formation. Loss-of-function of Susd4 in the mouse prevents long-term depression at cerebellar synapses, and leads to impairment in motor coordination adaptation and learning. Our findings reveal that activity-dependent synaptic plasticity relies on a transmembrane CCP domain-containing protein that regulates the degradation of specific substrates. This mechanism potentially accounts for the role of SUSD4 mutations in neurodevelopmental diseases.Competing Interest StatementThe authors have declared no competing interest.