RGD Reference Report - Synaptotagmin-3 drives AMPA receptor endocytosis, depression of synapse strength, and forgetting. - Rat Genome Database

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Synaptotagmin-3 drives AMPA receptor endocytosis, depression of synapse strength, and forgetting.

Authors: Awasthi, Ankit  Ramachandran, Binu  Ahmed, Saheeb  Benito, Eva  Shinoda, Yo  Nitzan, Noam  Heukamp, Alina  Rannio, Sabine  Martens, Henrik  Barth, Jonas  Burk, Katja  Wang, Yu Tian  Fischer, Andre  Dean, Camin 
Citation: Awasthi A, etal., Science. 2019 Jan 4;363(6422). pii: science.aav1483. doi: 10.1126/science.aav1483. Epub 2018 Dec 13.
RGD ID: 14697728
Pubmed: PMID:30545844   (View Abstract at PubMed)
DOI: DOI:10.1126/science.aav1483   (Journal Full-text)

Forgetting is important. Without it, the relative importance of acquired memories in a changing environment is lost. We discovered that synaptotagmin-3 (Syt3) localizes to postsynaptic endocytic zones and removes AMPA receptors from synaptic plasma membranes in response to stimulation. AMPA receptor internalization, long-term depression (LTD), and decay of long-term potentiation (LTP) of synaptic strength required calcium-sensing by Syt3 and were abolished through Syt3 knockout. In spatial memory tasks, mice in which Syt3 was knocked out learned normally but exhibited a lack of forgetting. Disrupting Syt3:GluA2 binding in a wild-type background mimicked the lack of LTP decay and lack of forgetting, and these effects were occluded in the Syt3 knockout background. Our findings provide evidence for a molecular mechanism in which Syt3 internalizes AMPA receptors to depress synaptic strength and promote forgetting.



Gene Ontology Annotations    Click to see Annotation Detail View

Molecular Function
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Gria2Ratprotein binding enablesIPIUniProtKB:P40748PMID:30545844IntAct 
Syt3Ratprotein binding enablesIPIUniProtKB:P19491PMID:30545844IntAct 

Objects Annotated

Genes (Rattus norvegicus)
Gria2  (glutamate ionotropic receptor AMPA type subunit 2)
Syt3  (synaptotagmin 3)


Additional Information