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Polo-like kinase 2 phosphorylation of amyloid precursor protein regulates activity-dependent amyloidogenic processing.


ABSTRACT: Alzheimer's disease (AD) is a neurodegenerative disorder with cognitive deficits. Amyloidogenic processing of amyloid precursor protein (APP) produces amyloid ? (A?), 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 ?-secretase at synapses and is required for neuronal overactivity-stimulated A? secretion. These findings implicate Plk2 as a novel mediator of activity-dependent APP amyloidogenic processing.

SUBMITTER: Lee Y 

PROVIDER: S-EPMC5414040 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature

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Polo-like kinase 2 phosphorylation of amyloid precursor protein regulates activity-dependent amyloidogenic processing.

Lee Yeunkum Y   Lee Ji Soo JS   Lee Kea Joo KJ   Turner R Scott RS   Hoe Hyang-Sook HS   Pak Daniel T S DTS  

Neuropharmacology 20170301


Alzheimer's disease (AD) is a neurodegenerative disorder with cognitive deficits. Amyloidogenic processing of amyloid precursor protein (APP) produces amyloid β (Aβ), 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-indu  ...[more]

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