| First Author | Zhang F | Year | 2017 |
| Journal | FASEB J | Volume | 31 |
| Issue | 10 | Pages | 4434-4446 |
| PubMed ID | 28646018 | Mgi Jnum | J:256414 |
| Mgi Id | MGI:6108482 | Doi | 10.1096/fj.201700346R |
| Citation | Zhang F, et al. (2017) The amyloid precursor protein modulates alpha2A-adrenergic receptor endocytosis and signaling through disrupting arrestin 3 recruitment. FASEB J 31(10):4434-4446 |
| abstractText | 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 alpha2A-adrenergic receptor (alpha2AAR) that occurs at the intracellular domains of both proteins. The APP interaction with alpha2AAR is promoted by agonist stimulation and competes with arrestin 3 binding to the receptor. Consequently, the presence of APP attenuates alpha2AAR 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 alpha2AAR activation. Concomitantly, agonist-induced internalization of alpha2AAR 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 alpha2AAR in controlling norepinephrine release and response, this novel regulation of alpha2AAR 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 alpha2A-adrenergic receptor endocytosis and signaling through disrupting arrestin 3 recruitment. |
