COMManDing lymphocyte migration (from Suzuki Lab, in JEM)
May 15, 2019
A research group of Kazuhiro Suzuki (Immune Response Dynamics, IFReC/RIMD, Osaka University) 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 migration. The COMMD 3/8 complex plays a crucial role in humoral immune responses and can be a drug target for the treatment of inflammatory diseases.
Fig. Proposed role of the COMMD3/8 complex in chemoattractant receptor signaling.
The COMMD3/8 complex recruits GRK6 to chemoattractant receptors through a stepwise mechanism: (i) the C-terminal tail of the activated receptor is phosphorylated by GRK2 and GRK3. (ii) the COMMD3/8 complex is associated with the receptor tail through electrostatic interactions with the phosphorylated residues. (iii) GRK6 is recruited to the receptor through the interaction with the COMMD3/8 complex and phosphorylates the C-terminal tail.
This article was published in the Journal of Experimental Medicine on May 14, 2019.
Title: The COMMD3/8 complex determines GRK6 specificity for chemoattractant receptors.
Authors: Akiko Nakai, Jun Fujimoto, Haruhiko Miyata, Ralf Stumm, Masashi Narazaki, Stefan Schulz, Yoshihiro Baba, Atsushi Kumanogoh, Kazuhiro Suzuki*. (*corresponding)