Amyloid precursor protein combinatorial phosphorylation code regulates AMPA receptor removal during distinct forms of synaptic plasticity.
Biochem Biophys Res Commun
; 709: 149803, 2024 May 21.
Article
en En
| MEDLINE
| ID: mdl-38552556
ABSTRACT
Synaptic plasticity is essential for memory encoding and stabilization of neural network activity. Plasticity is impaired in neurodegenerative conditions including Alzheimer disease (AD). A central factor in AD is amyloid precursor protein (APP). Previous studies have suggested APP involvement in synaptic plasticity, but physiological roles of APP are not well understood. Here, we identified combinatorial phosphorylation sites within APP that regulate AMPA receptor trafficking during different forms of synaptic plasticity. Dual phosphorylation sites at threonine-668/serine-675 of APP promoted endocytosis of the GluA2 subunit of AMPA receptors during homeostatic synaptic plasticity. APP was also required for GluA2 internalization during NMDA receptor-dependent long-term depression, albeit via a distinct pair of phosphoresidues at serine-655/threonine-686. These data implicate APP as a central gate for AMPA receptor internalization during distinct forms of plasticity, unlocked by specific combinations of phosphoresidues, and suggest that APP may serve broad functions in learning and memory.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Receptores AMPA
/
Enfermedad de Alzheimer
Límite:
Humans
Idioma:
En
Revista:
Biochem Biophys Res Commun
Año:
2024
Tipo del documento:
Article
País de afiliación:
Estados Unidos