Sie befinden Sich nicht im Netzwerk der Universität Paderborn. Der Zugriff auf elektronische Ressourcen ist gegebenenfalls nur via VPN oder Shibboleth (DFN-AAI) möglich. mehr Informationen...
SynGAP regulates synaptic plasticity and cognition independently of its catalytic activity
Ist Teil von
Science (American Association for the Advancement of Science), 2024-03, Vol.383 (6686), p.eadk1291
Ort / Verlag
United States: The American Association for the Advancement of Science
Erscheinungsjahr
2024
Link zum Volltext
Quelle
American Association for the Advancement of Science
Beschreibungen/Notizen
SynGAP is an abundant synaptic GTPase-activating protein (GAP) critical for synaptic plasticity, learning, memory, and cognition. Mutations in
in humans result in intellectual disability, autistic-like behaviors, and epilepsy. Heterozygous
-knockout mice display deficits in synaptic plasticity, learning, and memory and exhibit seizures. It is unclear whether SynGAP imparts structural properties at synapses independently of its GAP activity. Here, we report that inactivating mutations within the GAP domain do not inhibit synaptic plasticity or cause behavioral deficits. Instead, SynGAP modulates synaptic strength by physically competing with the AMPA-receptor-TARP excitatory receptor complex in the formation of molecular condensates with synaptic scaffolding proteins. These results have major implications for developing therapeutic treatments for
-related neurodevelopmental disorders.