Related Experiment Video
Updated: Jan 24, 2026
07:17
Measuring Composition of CD95 Death-Inducing Signaling Complex and Processing of Procaspase-8 in this Complex
Published on: August 2, 2021
2.9K
The COMMD3/8 complex determines GRK6 specificity for chemoattractant receptors
Akiko Nakai1, Jun Fujimoto1,2, Haruhiko Miyata3
1Laboratory of Immune Response Dynamics, Immunology Frontier Research Center, Osaka University, Osaka, Japan.
The Journal of Experimental Medicine
|May 16, 2019
Summary
The COMMD3/8 protein complex acts as an adaptor, selectively recruiting specific GPCR kinases (GRKs) to chemoattractant receptors. This targeted recruitment is crucial for regulating lymphocyte migration and immune responses.
Area of Science:
- Immunology
- Molecular Biology
- Cell Biology
Background:
- Lymphocyte migration relies on G protein-coupled receptors (GPCRs) activated by chemoattractants.
- GPCR kinases (GRKs) phosphorylate activated GPCRs, influencing downstream signaling via β-arrestins.
- The mechanism for targeting specific GRKs to activated GPCRs is not well understood.
Purpose of the Study:
- To identify the molecular machinery responsible for selective GRK targeting to GPCRs.
- To elucidate the role of identified components in lymphocyte migration and immune responses.
Main Methods:
- Protein complex identification and characterization.
- Analysis of protein recruitment to chemoattractant receptors.
- Assessment of B cell migration and humoral immune responses in deficient models.
- Biochemical assays using CXC-chemokine receptor 4 (CXCR4) as a model.
Main Results:
- A novel protein complex, COMMD3/8, was identified as a GRK adaptor.
- COMMD3/8 selectively recruits GRK6 to chemoattractant receptors, including CXCR4.
- COMMD3/8 deficiency impairs B cell migration and humoral immunity.
- GRK6-mediated phosphorylation of CXCR4 and subsequent β-arrestin signaling were demonstrated.
Conclusions:
- The COMMD3/8 complex determines GRK specificity for GPCRs.
- This complex represents a key regulatory point for immune responses.
- Targeting the COMMD3/8 complex could modulate lymphocyte function.
Related Concept Videos
01:31Internal Receptors
74.3K
Many cellular signals are hydrophilic and therefore cannot pass through the plasma membrane. However, small or hydrophobic signaling molecules can cross the hydrophobic core of the plasma membrane and bind to internal, or intracellular, receptors that reside within the cell. Many mammalian steroid hormones use this mechanism of cell signaling, as does nitric oxide (NO) gas.
74.3K
01:39Receptor-mediated Endocytosis
110.7K
Overview
110.7K
01:00Enzyme-linked Receptors
86.3K
Enzyme-linked receptors are proteins that act as both receptor and enzyme, activating multiple intracellular signals. This is a large group of receptors that include the receptor tyrosine kinase (RTK) family. Many growth factors and hormones bind to and activate the RTKs.
Neurotrophin (NT) receptors are a family of RTKs, including trkA, trkB, and trkC (tropomyosin-related kinase) receptors. TrkA is specific for nerve growth factor (NGF), neurotrophin-6, and neurotrophin-7. TrkB binds...
Neurotrophin (NT) receptors are a family of RTKs, including trkA, trkB, and trkC (tropomyosin-related kinase) receptors. TrkA is specific for nerve growth factor (NGF), neurotrophin-6, and neurotrophin-7. TrkB binds...
86.3K
02:41Protein Complex Assembly
16.7K
Proteins can form homomeric complexes with another unit of the same protein or heteromeric complexes with different types. Most protein complexes self-assemble spontaneously via ordered pathways, while some proteins need assembly factors that guide their proper assembly. Despite the crowded intracellular environment, proteins usually interact with their correct partners and form functional complexes.
Many viruses self-assemble into a fully functional unit using the infected host cell to...
Many viruses self-assemble into a fully functional unit using the infected host cell to...
16.7K
01:21G-protein Coupled Receptors
131.7K
G-protein coupled receptors are ligand binding receptors that indirectly affect changes in the cell. The actual receptor is a single polypeptide that transverses the cell membrane seven times creating intracellular and extracellular loops. The extracellular loops create a ligand specific pocket which binds to neurotransmitters or hormones. The intracellular loops holds onto the G-protein.
131.7K
01:57Protein Complexes with Interchangeable Parts
2.9K
Groups of proteins may form a complex where each protein in this complex has a different role in the overall execution of the complex’s function. Often some of the proteins in the complex can be replaced by a closely related variant to give a complex that contains many of the same components yet is functionally distinct.
The SCF ubiquitin ligase is a protein complex of five individual proteins. This complex attaches ubiquitin to other target proteins to mark them for degradation. In order...
The SCF ubiquitin ligase is a protein complex of five individual proteins. This complex attaches ubiquitin to other target proteins to mark them for degradation. In order...
2.9K