Internal medicine

Vesicle

Neuroscience

Receptor

Disease

Amyloid precursor protein

Membrane

Biology

Ectodomain

GABAB receptor

Synaptic vesicle

GABAA receptor

Metabotropic receptor

Neurotransmitter

Chemistry

Neurotransmission

Cell biology

Synaptic plasticity

Alzheimer's disease

Biochemistry

Glutamate receptor

Medicine

Science

A physiological function for sAPP? Although the pathological role of the amyloid-β precursor protein (APP) in Alzheimer's disease is well studied, the physiological role of this protein has remained elusive. Rice et al. found that the secreted ectodomain of APP (sAPP) binds to GABA B R1a, the metabotropic receptor for the inhibitory neurotransmitter γ-aminobutyric acid (GABA) (see the Perspective by Korte). Binding suppressed synaptic vesicle release and modulated synaptic transmission and plasticity in mice. A short, 17–amino acid peptide in APP bound to GABA B R1a's sushi 1 domain, conferring structure to this unstructured domain. Therapeutics targeting this interaction could potentially benefit a range of neurological disorders in which GABA signaling is implicated. Science , this issue p. eaao4827 ; see also p. 123

Secreted amyloid-β precursor protein functions as a GABA <sub>B</sub> R1a ligand to modulate synaptic transmission

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

Secreted amyloid-β precursor protein functions as a GABA _B R1a ligand to modulate synaptic transmission