| Literature DB >> 30630900 |
Heather C Rice1,2, Daniel de Malmazet3,4, An Schreurs5, Samuel Frere6, Inge Van Molle7, Alexander N Volkov7,8, Eline Creemers1,2, Irena Vertkin6, Julie Nys1,2, Fanomezana M Ranaivoson9, Davide Comoletti9,10, Jeffrey N Savas11, Han Remaut7, Detlef Balschun5, Keimpe D Wierda1,2, Inna Slutsky6, Karl Farrow3,4,12,13, Bart De Strooper14,2,15, Joris de Wit14,2.
Abstract
Amyloid-β precursor protein (APP) is central to the pathogenesis of Alzheimer's disease, yet its physiological function remains unresolved. Accumulating evidence suggests that APP has a synaptic function mediated by an unidentified receptor for secreted APP (sAPP). Here we show that the sAPP extension domain directly bound the sushi 1 domain specific to the γ-aminobutyric acid type B receptor subunit 1a (GABABR1a). sAPP-GABABR1a binding suppressed synaptic transmission and enhanced short-term facilitation in mouse hippocampal synapses via inhibition of synaptic vesicle release. A 17-amino acid peptide corresponding to the GABABR1a binding region within APP suppressed in vivo spontaneous neuronal activity in the hippocampus of anesthetized Thy1-GCaMP6s mice. Our findings identify GABABR1a as a synaptic receptor for sAPP and reveal a physiological role for sAPP in regulating GABABR1a function to modulate synaptic transmission.Entities:
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Year: 2019 PMID： 30630900 PMCID： PMC6366617 DOI： 10.1126/science.aao4827
Source DB: PubMed Journal: Science ISSN： 0036-8075 Impact factor: 47.728