Polo-like kinase 2 phosphorylation of amyloid precursor protein regulates activity-dependent amyloidogenic processing.
Neuropharmacology
; 117: 387-400, 2017 05 01.
Article
en En
| MEDLINE
| ID: mdl-28257888
ABSTRACT
Alzheimer's disease (AD) is a neurodegenerative disorder with cognitive deficits. Amyloidogenic processing of amyloid precursor protein (APP) produces amyloid ß (Aß), the major component of hallmark AD plaques. Synaptic activity stimulates APP cleavage, whereas APP promotes excitatory synaptic transmission, suggesting APP participates in neuronal homeostasis. However, mechanisms linking synaptic activity to APP processing are unclear. Here we show that Polo-like kinase 2 (Plk2), an activity-inducible regulator of homeostatic plasticity, directly binds and phosphorylates threonine-668 and serine-675 of APP in vitro and associates with APP in vivo. Plk2 accelerates APP amyloidogenic cleavage by ß-secretase at synapses and is required for neuronal overactivity-stimulated Aß secretion. These findings implicate Plk2 as a novel mediator of activity-dependent APP amyloidogenic processing.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Precursor de Proteína beta-Amiloide
/
Proteínas Serina-Treonina Quinasas
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Neuropharmacology
Año:
2017
Tipo del documento:
Article
País de afiliación:
Corea del Sur