Secreted amyloid-β precursor protein functions as a GABA<sub>B</sub>R1a ligand to modulate synaptic transmission.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 30630900.
- Also identified by DOI 10.1126/science.aao4827 and PMC identifier 6366617.
- No licence information is recorded for this record.
- Because redistribution is not established, this page shows the abstract only. Follow the links below for the full text.
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 (GABA<sub>B</sub>R1a). sAPP-GABA<sub>B</sub>R1a 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 GABA<sub>B</sub>R1a binding region within APP suppressed in vivo spontaneous neuronal activity in the hippocampus of anesthetized Thy1-GCaMP6s mice. Our findings identify GABA<sub>B</sub>R1a as a synaptic receptor for sAPP and reveal a physiological role for sAPP in regulating GABA<sub>B</sub>R1a function to modulate synaptic transmission.
Medical subject headings
- Amyloid beta-Protein Precursor
- Neuronal Plasticity
- Receptors, GABA-A
- Synaptic Transmission