The amyloid precursor protein modulates α_2A-adrenergic receptor endocytosis and signaling through disrupting arrestin 3 recruitment.

ABSTRACT: The amyloid precursor protein (APP) has long been appreciated for its role in Alzheimer's disease (AD) pathology. However, less is known about the physiologic function of APP outside of AD. Particularly, whether and how APP may regulate functions of cell surface receptors, including GPCRs, remains largely unclear. In this study, we identified a novel direct interaction between APP and the α_2A-adrenergic receptor (α_2AAR) that occurs at the intracellular domains of both proteins. The APP interaction with α_2AAR is promoted by agonist stimulation and competes with arrestin 3 binding to the receptor. Consequently, the presence of APP attenuates α_2AAR internalization and desensitization, which are arrestin-dependent processes. Furthermore, in neuroblas

SUBMITTER: Zhang F 

PROVIDER: S-EPMC5602903 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature