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Secreted amyloid-b precursor protein functions as a GABA B R1a ligand to modulate synaptic transmission

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journal contribution
posted on 04.08.2022, 22:23 authored by HC Rice, D De Malmazet, A Schreurs, S Frere, I Van Molle, AN Volkov, E Creemers, I Vertkin, J Nys, FM Ranaivoson, Davide ComolettiDavide Comoletti, JN Savas, H Remaut, D Balschun, KD Wierda, I Slutsky, K Farrow, B De Strooper, J De Wit
Amyloid-b 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 g-aminobutyric acid type B receptor subunit 1a (GABA B R1a). sAPP-GABA B 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 B R1a binding region within APP suppressed in vivo spontaneous neuronal activity in the hippocampus of anesthetized Thy1-GCaMP6s mice. Our findings identify GABA B R1a as a synaptic receptor for sAPP and reveal a physiological role for sAPP in regulating GABA B R1a function to modulate synaptic transmission.

Funding

Collaborative Research: Structure and Function of Reelin in Brain Development | Funder: RUTGERS UNIVERSITY | Grant ID: 1755189

History

Preferred citation

Rice, H. C., De Malmazet, D., Schreurs, A., Frere, S., Van Molle, I., Volkov, A. N., Creemers, E., Vertkin, I., Nys, J., Ranaivoson, F. M., Comoletti, D., Savas, J. N., Remaut, H., Balschun, D., Wierda, K. D., Slutsky, I., Farrow, K., De Strooper, B. & De Wit, J. (2019). Secreted amyloid-b precursor protein functions as a GABA B R1a ligand to modulate synaptic transmission. Science, 363(6423), 143-143. https://doi.org/10.1126/science.aao4827

Journal title

Science

Volume

363

Issue

6423

Publication date

11/01/2019

Pagination

143-143

Publisher

American Association for the Advancement of Science (AAAS)

Publication status

Published

ISSN

0036-8075

eISSN

1095-9203

Article number

ARTN eaao4827

Language

en