| First Author | Wu Y | Year | 2020 |
| Journal | Mol Cell | Volume | 78 |
| Issue | 1 | Pages | 42-56.e6 |
| PubMed ID | 32035036 | Mgi Jnum | J:287739 |
| Mgi Id | MGI:6406609 | Doi | 10.1016/j.molcel.2020.01.022 |
| Citation | Wu Y, et al. (2020) Dopamine Uses the DRD5-ARRB2-PP2A Signaling Axis to Block the TRAF6-Mediated NF-kappaB Pathway and Suppress Systemic Inflammation. Mol Cell 78(1):42-56.e6 |
| abstractText | The functional relevance and mechanistic basis of the effects of the neurotransmitter dopamine (DA) on inflammation remain unclear. Here we reveal that DA inhibited TLR2-induced NF-kappaB activation and inflammation via the DRD5 receptor in macrophages. We found that the DRD5 receptor, via the EFD and IYX(X)I/L motifs in its CT and IC3 loop, respectively, can directly recruit TRAF6 and its negative regulator ARRB2 to form a multi-protein complex also containing downstream signaling proteins, such as TAK1, IKKs, and PP2A, that impairs TRAF6-mediated activation of NF-kappaB and expression of pro-inflammatory genes. Furthermore, the DA-DRD5-ARRB2-PP2A signaling axis can prevent S. aureus-induced inflammation and protect mice against S. aureus-induced sepsis and meningitis after DA treatment. Collectively, these findings provide the first demonstration of DA-DRD5 signaling acting to control inflammation and a detailed delineation of the underlying mechanism and identify the DRD5-ARRB2-PP2A axis as a potential target for future therapy of inflammation-associated diseases such as meningitis and sepsis. |
