doi: 10.1126/scisignal.3115pe12.
GPCR dimers fall apart
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- PMID:20354223
- PMCID: PMC3930916
- DOI: 10.1126/scisignal.3115pe12
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GPCR dimers fall apart
Nevin A Lambert. Sci Signal..
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Abstract
G protein-coupled receptors (GPCRs), also known as seven-transmembrane receptors (7TMRs), transduce various sensory and nonsensory signals. It is now widely accepted that these receptors associate with each other as homomeric or heteromeric dimers or as higher-order oligomers. This realization raises a number of questions regarding the quaternary structure of GPCRs and the function of GPCR oligomers: How does ligand binding in one protomer affect an associated protomer? What is the functional unit that activates downstream signaling molecules? What parts of the receptor form the interfaces between protomers? Where along the pathway from synthesis to degradation do oligomers form? Do they ever dissociate? Until recently, this last question has attracted little attention, and GPCR dimers and oligomers have generally been considered to be stable structures. However, biophysical studies have now begun to address this question, and the answer that is emerging will require a reassessment of the stable dimer model.
Figures
(A) Some class A GPCRs exist at the plasma membrane in a monomer-dimer equilibrium. The traditional view of GPCRs as freely diffusing monomers (left) and the newer view of GPCRs as dimers (right) are both accommodated by a dynamic equilibrium. The rate of dimer association (k1) will depend on the local concentration of monomers and time, whereas the rate of dimer dissociation (k−1) will depend only on time. Both rates might be altered by cellular factors such as lipid composition, the presence of ligands, and other factors. (B) A top-down view of GPCRs diffusing on the cell surface, such as in the experiments of Hernet al. (6). Two receptors labeled with differently colored ligands take separate random walks in the plasma membrane until they encounter each other (left) and (in some cases) associate. The two receptors diffuse together as a dimer (yellow track) until they dissociate (right) and go their separate ways. In the experiments of Hernet al., dimers existed for ~0.5 s on average, and ~30% of the receptors were dimers at any given instant.
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