Synergetic Roles of Formyl Peptide Receptor 1 Oligomerization in Ligand-Induced Signal Transduction. 2020

Tomoki Nishiguchi, and Hideaki Yoshimura, and Rinshi S Kasai, and Takahiro K Fujiwara, and Takeaki Ozawa
School of Science, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.

G 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.

UI MeSH Term Description Entries
D008024 Ligands A molecule that binds to another molecule, used especially to refer to a small molecule that binds specifically to a larger molecule, e.g., an antigen binding to an antibody, a hormone or neurotransmitter binding to a receptor, or a substrate or allosteric effector binding to an enzyme. Ligands are also molecules that donate or accept a pair of electrons to form a coordinate covalent bond with the central metal atom of a coordination complex. (From Dorland, 27th ed) Ligand
D008856 Microscopy, Fluorescence Microscopy of specimens stained with fluorescent dye (usually fluorescein isothiocyanate) or of naturally fluorescent materials, which emit light when exposed to ultraviolet or blue light. Immunofluorescence microscopy utilizes antibodies that are labeled with fluorescent dye. Fluorescence Microscopy,Immunofluorescence Microscopy,Microscopy, Immunofluorescence,Fluorescence Microscopies,Immunofluorescence Microscopies,Microscopies, Fluorescence,Microscopies, Immunofluorescence
D011485 Protein Binding The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments. Plasma Protein Binding Capacity,Binding, Protein
D005456 Fluorescent Dyes Chemicals that emit light after excitation by light. The wave length of the emitted light is usually longer than that of the incident light. Fluorochromes are substances that cause fluorescence in other substances, i.e., dyes used to mark or label other compounds with fluorescent tags. Flourescent Agent,Fluorescent Dye,Fluorescent Probe,Fluorescent Probes,Fluorochrome,Fluorochromes,Fluorogenic Substrates,Fluorescence Agents,Fluorescent Agents,Fluorogenic Substrate,Agents, Fluorescence,Agents, Fluorescent,Dyes, Fluorescent,Probes, Fluorescent,Substrates, Fluorogenic
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D015398 Signal Transduction The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway. Cell Signaling,Receptor-Mediated Signal Transduction,Signal Pathways,Receptor Mediated Signal Transduction,Signal Transduction Pathways,Signal Transduction Systems,Pathway, Signal,Pathway, Signal Transduction,Pathways, Signal,Pathways, Signal Transduction,Receptor-Mediated Signal Transductions,Signal Pathway,Signal Transduction Pathway,Signal Transduction System,Signal Transduction, Receptor-Mediated,Signal Transductions,Signal Transductions, Receptor-Mediated,System, Signal Transduction,Systems, Signal Transduction,Transduction, Signal,Transductions, Signal
D044042 Receptors, Formyl Peptide A family of G-protein-coupled receptors that was originally identified by its ability to bind N-formyl peptides such as N-FORMYLMETHIONINE LEUCYL-PHENYLALANINE. Since N-formyl peptides are found in MITOCHONDRIA and BACTERIA, this class of receptors is believed to play a role in mediating cellular responses to cellular damage and bacterial invasion. However, non-formylated peptide ligands have also been found for this receptor class. Chemotactic Peptide Receptor,Chemoattractant Receptor,F-Chemotactic Peptide Receptor,FMLP Receptor,Formyl Peptide Receptor,N-Formylmethionyl Peptide Receptor,N-formyl Hexapeptide Receptor,Receptor, Chemotactic Peptide,fMet-Leu-Phe Receptor,F Chemotactic Peptide Receptor,Formyl Peptide Receptors,Hexapeptide Receptor, N-formyl,N Formylmethionyl Peptide Receptor,N formyl Hexapeptide Receptor,Peptide Receptor, Chemotactic,Peptide Receptor, N-Formylmethionyl,Peptide Receptors, Formyl,Receptor, Chemoattractant,Receptor, F-Chemotactic Peptide,Receptor, FMLP,Receptor, Formyl Peptide,Receptor, N-Formylmethionyl Peptide,Receptor, N-formyl Hexapeptide,Receptor, fMet-Leu-Phe,fMet Leu Phe Receptor
D055503 Protein Multimerization The assembly of the QUATERNARY PROTEIN STRUCTURE of multimeric proteins (MULTIPROTEIN COMPLEXES) from their composite PROTEIN SUBUNITS. Protein Dimerization,Protein Heteromultimerizaton,Protein Multimer Assembly,Protein Trimerization,Assembly, Protein Multimer,Dimerization, Protein,Heteromultimerizaton, Protein,Heteromultimerizatons, Protein,Multimer Assembly, Protein,Multimerization, Protein,Trimerization, Protein
D057809 HEK293 Cells A cell line generated from human embryonic kidney cells that were transformed with human adenovirus type 5. 293T Cells,HEK 293 Cell Line,HEK 293 Cells,Human Embryonic Kidney Cell Line 293,Human Kidney Cell Line 293,293 Cell, HEK,293 Cells, HEK,293T Cell,Cell, 293T,Cell, HEK 293,Cell, HEK293,Cells, 293T,Cells, HEK 293,Cells, HEK293,HEK 293 Cell,HEK293 Cell
D059010 Single-Cell Analysis Assaying the products of or monitoring various biochemical processes and reactions in an individual cell. Analyses, Single-Cell,Analysis, Single-Cell,Single Cell Analysis,Single-Cell Analyses

Related Publications

Tomoki Nishiguchi, and Hideaki Yoshimura, and Rinshi S Kasai, and Takahiro K Fujiwara, and Takeaki Ozawa
December 2008, Bioconjugate chemistry,
Tomoki Nishiguchi, and Hideaki Yoshimura, and Rinshi S Kasai, and Takahiro K Fujiwara, and Takeaki Ozawa
May 1992, The Biochemical journal,
Tomoki Nishiguchi, and Hideaki Yoshimura, and Rinshi S Kasai, and Takahiro K Fujiwara, and Takeaki Ozawa
November 1988, Trends in biochemical sciences,
Tomoki Nishiguchi, and Hideaki Yoshimura, and Rinshi S Kasai, and Takahiro K Fujiwara, and Takeaki Ozawa
September 1985, The Journal of biological chemistry,
Tomoki Nishiguchi, and Hideaki Yoshimura, and Rinshi S Kasai, and Takahiro K Fujiwara, and Takeaki Ozawa
November 2004, Molecular pharmacology,
Tomoki Nishiguchi, and Hideaki Yoshimura, and Rinshi S Kasai, and Takahiro K Fujiwara, and Takeaki Ozawa
March 2002, The Journal of biological chemistry,
Tomoki Nishiguchi, and Hideaki Yoshimura, and Rinshi S Kasai, and Takahiro K Fujiwara, and Takeaki Ozawa
November 1994, Trends in biochemical sciences,
Tomoki Nishiguchi, and Hideaki Yoshimura, and Rinshi S Kasai, and Takahiro K Fujiwara, and Takeaki Ozawa
January 1998, Cytokine & growth factor reviews,
Tomoki Nishiguchi, and Hideaki Yoshimura, and Rinshi S Kasai, and Takahiro K Fujiwara, and Takeaki Ozawa
December 2001, Proceedings of the National Academy of Sciences of the United States of America,
Tomoki Nishiguchi, and Hideaki Yoshimura, and Rinshi S Kasai, and Takahiro K Fujiwara, and Takeaki Ozawa
July 2017, Scientific reports,
Copied contents to your clipboard!