cb0c00631_si_001.pdf (1.43 MB)
Synergetic Roles of Formyl Peptide Receptor 1 Oligomerization in Ligand-Induced Signal Transduction
journal contribution
posted on 2020-09-07, 07:11 authored by Tomoki Nishiguchi, Hideaki Yoshimura, Rinshi S. Kasai, Takahiro K. Fujiwara, Takeaki OzawaG protein-coupled
receptors (GPCRs) transduce extracellular signals
into cells by interacting with G proteins and arrestins. Emerging
evidence suggests that GPCRs on the plasma membrane are in a dynamic
equilibrium among monomers, dimers, and larger oligomers. Nevertheless,
the role of the oligomer formation in the GPCR signal transduction
remains unclear. Using multicolor single-molecule live-cell imaging,
we show a dynamic interconversion between small and large oligomer
states of a chemoattractant GPCR, Formyl Peptide Receptor 1 (FPR1),
and its binding affinity with G protein. Full agonist stimulation
increased a fraction of large FPR1 oligomers, which allowed for prolonged
FPR1-G protein interaction. The G protein interaction with FPR1 was
most stabilized at the full agonist-bound large FPR1 oligomers. Based
on these results, we propose that G protein-mediated signal transduction
may be regulated synergistically by the ligand-binding and FPR1 oligomerization.
Cooperative signal control induced by receptor oligomerization is
anticipated as a target for drug discovery.
History
Usage metrics
Categories
Keywords
FPR 1 oligomersoligomer statesFPR 1 oligomerizationplasma membranebinding affinityFormyl Peptide Receptor 1G protein interactionchemoattractant GPCRFormyl Peptide Receptor 1 Oligomeri...G protein-mediated signal transductionFPR 1-G protein interactionCooperative signal controlLigand-Induced Signal Transduction ...oligomer formationdrug discoverytransduce extracellular signalsFPR 1Full agonist stimulationG proteinG proteinssingle-molecule live-cell imagingSynergetic Rolesreceptor oligomerizationGPCR signal transduction
Licence
Exports
RefWorks
BibTeX
Ref. manager
Endnote
DataCite
NLM
DC