| First Author | Nakai A | Year | 2019 |
| Journal | J Exp Med | Volume | 216 |
| Issue | 7 | Pages | 1630-1647 |
| PubMed ID | 31088898 | Mgi Jnum | J:278399 |
| Mgi Id | MGI:6342394 | Doi | 10.1084/jem.20181494 |
| Citation | Nakai A, et al. (2019) The COMMD3/8 complex determines GRK6 specificity for chemoattractant receptors. J Exp Med 216(7):1630-1647 |
| abstractText | Lymphocyte migration is mediated by G protein-coupled receptors (GPCRs) that respond to chemoattractive molecules. After their activation, GPCRs are phosphorylated by different GPCR kinases (GRKs), which produces distinct functional outcomes through beta-arrestins. However, the molecular machinery that targets individual GRKs to activated GPCRs remains elusive. Here, we identified a protein complex consisting of copper metabolism MURR1 domain-containing (COMMD) 3 and COMMD8 (COMMD3/8 complex) as an adaptor that selectively recruits a specific GRK to chemoattractant receptors and promotes lymphocyte chemotaxis. COMMD8, whose stability depended on COMMD3, was recruited to multiple chemoattractant receptors. Deficiency of COMMD8 or COMMD3 impaired B cell migration and humoral immune responses. Using CXC-chemokine receptor 4 (CXCR4) as a model, we demonstrated that the COMMD3/8 complex selectively recruited GRK6 and induced GRK6-mediated phosphorylation of the receptor and activation of beta-arrestin-mediated signaling. Thus, the COMMD3/8 complex is a specificity determinant of GRK targeting to GPCRs and represents a point of regulation for immune responses. |
