| First Author | Rice HC | Year | 2019 |
| Journal | Science | Volume | 363 |
| Issue | 6423 | PubMed ID | 30630900 |
| Mgi Jnum | J:273342 | Mgi Id | MGI:6281049 |
| Doi | 10.1126/science.aao4827 | Citation | Rice HC, et al. (2019) Secreted amyloid-beta precursor protein functions as a GABABR1a ligand to modulate synaptic transmission. Science 363(6423) |
| abstractText | Amyloid-beta 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 gamma-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. |
