The amyloid precursor protein modulates {alpha}2A-adrenergic receptor endocytosis and signaling through disrupting arrestin 3 recruitment [Research]

In this study, we identified a novel direct interaction between APP and the α2A-adrenergic receptor (α2AAR) that occurs at the intracellular domains of both proteins. The APP interaction with α2AAR is promoted by agonist stimulation and competes with arrestin 3 binding to the receptor. Consequently, the presence of APP attenuates α2AAR internalization and desensitization, which are arrestin-dependent processes. Furthermore, in neuroblastoma neuro-2A cells and primary superior cervical ganglion neurons, where APP is highly expressed, the lack of APP leads to a dramatic increase in plasma membrane recruitment of endogenous arrestin 3 following α2AAR activation. Concomitantly, agonist-induced internalization of α2AAR is significantly enhanced in these neuronal cells. Our study provided the first evidence that APP fine tunes GPCR signaling and trafficking. Given the important role of α2AAR in controlling norepinephrine release and response, this novel regulation of α2AAR by APP may have an impact on modulation of noradrenergic activity and sympathetic tone.—Zhang, F., Gannon, M., Chen, Y., Zhou, L., Jiao, K., Wang, Q. The amyloid precursor protein modulates α2A-adrenergic receptor endocytosis and signaling through disrupting arrestin 3 recruitment.

Source: FASEB Journal - September 28, 2017 Category: Biology Authors: Zhang, F., Gannon, M., Chen, Y., Zhou, L., Jiao, K., Wang, Q. Tags: Research Source Type: research