The Evolution of the GPCR Signaling System in Eukaryotes: Modularity, Conservation, and the Transition to Metazoan Multicellularity
Alex de Mendoza,Arnau Sebé-Pedrós,Arnau Sebé-Pedrós,Iñaki Ruiz-Trillo,Iñaki Ruiz-Trillo,Iñaki Ruiz-Trillo +5 more
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TLDR
Using eukaryotic genomes covering most lineages sampled to date, it is found that the various components of the GPCR signaling pathway evolved independently, highlighting the modular nature of this system.Abstract:
The G-protein-coupled receptor (GPCR) signaling system is one of the main signaling pathways in eukaryotes. Here, we analyze the evolutionary history of all its components, from receptors to regulators, to gain a broad picture of its system-level evolution. Using eukaryotic genomes covering most lineages sampled to date, we find that the various components of the GPCR signaling pathway evolved independently, highlighting the modular nature of this system. Our data show that some GPCR families, G proteins, and regulators of G proteins diversified through lineage-specific diversifications and recurrent domain shuffling. Moreover, most of the gene families involved in the GPCR signaling system were already present in the last common ancestor of eukaryotes. Furthermore, we show that the unicellular ancestor of Metazoa already had most of the cytoplasmic components of the GPCR signaling system, including, remarkably, all the G protein alpha subunits, which are typical of metazoans. Thus, we show how the transition to multicellularity involved conservation of the signaling transduction machinery, as well as a burst of receptor diversification to cope with the new multicellular necessities.read more
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The Diverse Roles of Arrestin Scaffolds in G Protein-Coupled Receptor Signaling.
TL;DR: The structure–function relationships that enable arrestins to perform their diverse roles are examined, addressing arrestin structure at the molecular level, the relationship between arrestin conformation and function, and sites of interaction between arrestins, GPCRs, and nonreceptor-binding partners.
Journal ArticleDOI
Selectivity determinants of GPCR–G-protein binding
TL;DR: The existence of a selectivity barcode on each of the 16 human G proteins that is recognized by distinct regions on the approximately 800 human receptors is revealed, laying the foundation for understanding the molecular basis of coupling selectivity within individual receptors and G proteins.
Journal ArticleDOI
Single-cell transcriptomics of the human placenta: inferring the cell communication network of the maternal-fetal interface.
Mihaela Pavlicev,Günter P. Wagner,Arun R. Chavan,Kathryn Owens,Jamie Maziarz,Caitlin E. Dunn-Fletcher,Suhas G. Kallapur,Suhas G. Kallapur,Louis J. Muglia,Louis J. Muglia,Helen Jones,Helen Jones +11 more
TL;DR: This work studied the cell-cell interactome of fetal placental trophoblast cells and maternal endometrial stromal cells, using single-cell transcriptomics and finds a highly cell-type-specific expression of G-protein-coupled receptors, implying that ligand-receptor profiles could be a reliable tool for cell type identification.
Journal ArticleDOI
Manifold roles of β-arrestins in GPCR signaling elucidated with siRNA and CRISPR/Cas9
Louis M. Luttrell,Louis M. Luttrell,Jialu Wang,Bianca Plouffe,Jeffrey S. Smith,Lama Yamani,Suneet Kaur,Pierre Yves Jean-Charles,Christophe Gauthier,Mi Hye Lee,Biswaranjan Pani,Jihee Kim,Seungkirl Ahn,Sudarshan Rajagopal,Eric Reiter,Michel Bouvier,Sudha K. Shenoy,Stéphane A. Laporte,Howard A. Rockman,Robert J. Lefkowitz,Robert J. Lefkowitz +20 more
TL;DR: The data suggest that β-arrestins function as a regulatory hub, determining the balance between mechanistically different pathways that result in activation of ERK1/2, and caution against extrapolating results obtained from βArr 1/2- or G protein–deleted cells to GPCR behavior in native systems.
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