G protein-coupled receptors articles within Nature Communications

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  • Article
    | Open Access

    PDZ domain-containing proteins are known to function as intracellular scaffolds. Here, Egea-Jimenez et al. report the structure of the tandem PDZ domains of syntenin in complex with a Frizzled 7 peptide and PIP2, show that the ligands bind to syntenin cooperatively and illustrate the role of the complex for Frizzled 7 function.

    • Antonio Luis Egea-Jimenez
    • , Rodrigo Gallardo
    •  & Pascale Zimmermann

  • Article
    | Open Access

    FLRT proteins are known to interact with Lphns and Unc5s, mediating cell adhesion and repulsion respectively. Here the authors use crystallography, native mass spectrometry, molecular dynamics simulations and cell-based assays to show that these three proteins form large super-complexes with functions distinct from their smaller subcomplexes.

    • Verity A. Jackson
    • , Shahid Mehmood
    •  & Elena Seiradake

  • Article
    | Open Access

    The mechanism by which relaxin activates the relaxin family peptide receptor-1 is poorly understood. Here, Sethi et al.identify a relaxin binding site in an extracellular linker between the LDLa and LRR domains and propose that relaxin binding stabilizes a helical conformation that leads to receptor activation.

    • Ashish Sethi
    • , Shoni Bruell
    •  & Paul R. Gooley

  • Article
    | Open Access

    Microglia play key roles during early neurodevelopment. Here the authors show that microglia are important mediators of ocular dominance plasticity (ODP). Microglia respond to monocular deprivation during the visual critical period, and disrupting microglial P2Y12 purinergic receptor abrogates ODP.

    • G. O. Sipe
    • , R. L. Lowery,
    •  & A. K. Majewska

  • Article
    | Open Access

    Protease-activated-receptor 1 and 2 (PAR1 and PAR2) are key players in tumor growth. In this study, the authors identify PAR1 and PAR2 domains that bind oncogenic signalling proteins driving breast cancer progression in vivo and placental extravillous trophoblast invasion in vitro.

    • A. Kancharla
    • , M. Maoz
    •  & R. Bar-Shavit

  • Article
    | Open Access

    Little is known regarding migration of Th17 cells that produce distinct cytokines implicated in protection and pathology. Kara et al. show that a switch from CCR6 to CCR2 by Th17 cells defines a signature (CCR6−CCR2+) of GM-CSF+Th17 cells and drives pathology in a mouse model of autoimmunity.

    • Ervin E. Kara
    • , Duncan R. McKenzie
    •  & Shaun R. McColl

  • Article
    | Open Access

    Optogenetic activation of β2-adrenergic receptors (β2-AR) has been achieved, but not characterized in detail. Here, Siudaet al. show that light-controlled opto-β2AR mimics endogenous β2AR activity in vitro and in vivo, and develop novel, optically active, functionally selective receptors to bias β2AR intracellular signaling mechanisms.

    • Edward R. Siuda
    • , Jordan G. McCall
    •  & Michael R. Bruchas

  • Article
    | Open Access

    The function of memory CD8+ T cells is often believed to be directly correlated with their localization in tissues. Here the authors show that CD8+T cells with different proliferative and cytotoxic properties can be distinguished based on their expression of CX3CR1, independently of their tissue localization.

    • Jan P. Böttcher
    • , Marc Beyer
    •  & Percy A. Knolle

  • Article
    | Open Access

    The sphingolipid sphingosine-1-phosphate (S1P) plays a vital role in vascular homeostasis through the interaction with its receptors S1PR1-5. Here, by using genetic and pharmacological approaches, the authors show that S1PR2-mediated signaling is crucial for the disruption of cerebrovascular integrity and development of intracerebral haemorrhage in a mouse stroke model.

    • Gab Seok Kim
    • , Li Yang
    •  & Teresa Sanchez

  • Article
    | Open Access

    G protein-coupled receptors (GPCRs) are the largest family of transmembrane signaling proteins in humans and exhibit diverse activation mechanisms. Here, the authors combine electron microscopy, hydrogen deuterium exchange and Molecular dynamics simulations to gain insight into the activation mechanism of the glucagon receptor.

    • Linlin Yang
    • , Dehua Yang
    •  & Hualiang Jiang

  • Article
    | Open Access

    The structural basis of how G-protein coupled receptors respond to unique stimuli remains poorly understood. Here, Krumm et al.present new structures of the neurotensin receptor and reveal insights into how ligand binding is linked to structural rearrangements associated with receptor activation.

    • Brian E. Krumm
    • , Jim F. White
    •  & Reinhard Grisshammer

  • Article
    | Open Access

    Fatty acids are ancient lipids with numerous functions, from metabolic processes as a source of energy to structural and signalling roles within cell membranes. Here, the authors present azobenzene-modified fatty acids and their application as photoswitchable agonists of the Vanilloid Receptor 1.

    • James Allen Frank
    • , Mirko Moroni
    •  & Dirk Trauner

  • Article
    | Open Access

    Mutations in GPR56, a member of the adhesion G protein-coupled receptor family, cause a specific human brain malformation and myelination defects but the cellular causes remain unclear. Here the authors show that loss of Gpr56in mice leads to decreased oligodendrocyte precursor cell proliferation and diminished levels of active RhoA.

    • Stefanie Giera
    • , Yiyu Deng
    •  & Xianhua Piao

  • Article |

    The adhesion class of G protein-coupled receptors (aGPCRs) is essential for peripheral nervous system myelination, but functions in central nervous system myelination are less understood. Here the authors show that the aGPCR Gpr56 plays a role in the development of myelinating oligodendrocytes and that this function is mediated by Gα12/13 proteins and Rho activation.

    • Sarah D. Ackerman
    • , Cynthia Garcia
    •  & Kelly R. Monk

  • Article |

    Understanding the molecular basis of receptor activation requires characterizing the dynamic equilibrium of conformational states. Here the authors show that the metabotropic glutamate receptor oscillates between conformations on a sub-millisecond timescale, and agonists quantitatively shift the equilibrium towards the activated state based on their potency.

    • Linnea Olofsson
    • , Suren Felekyan
    •  & Emmanuel Margeat

  • Article |

    Opsin has recently been shown to equilibrate phospholipids across the photoreceptor disc membranes. Goren et al.demonstrate that the large conformational changes driven by exposure to light are not required for this activity, and provide insight into the potential mechanisms of lipid translocation.

    • Michael A. Goren
    • , Takefumi Morizumi
    •  & Anant K. Menon

  • Article |

    The crystal structure of the A2A GPCR suggested that water molecules might form a continuous pathway that becomes disrupted during receptor activation. Here Yuan et al.instead show that a conserved layer of hydrophobic residues forms a gate that opens to form a continuous water channel upon receptor activation.

    • Shuguang Yuan
    • , Slawomir Filipek
    •  & Horst Vogel

  • Article |

    Following their internalization, G protein-coupled receptors may continue to signal from endosomes through downstream proteins such as Gαs. Rosciglione et al. reveal that Gαsalso regulates the onward trafficking of these receptors from endosomes to lysosomes by interacting with components of the ESCRT complex.

    • Stéphanie Rosciglione
    • , Caroline Thériault
    •  & Christine Lavoie

  • Article
    | Open Access

    G-protein coupled receptors can signal through G-proteins or through β-arrestin, however mechanisms determining pathway selection remain unclear. Here the authors show that the duration of cannabinoid receptor clustering in clathrin coated pits prior to endocytosis determines the strength of β-arrestin signalling.

    • Jacqueline Flores-Otero
    • , Kwang H. Ahn
    •  & Guillermo A. Yudowski

  • Article |

    The Wnt receptor Frizzled binds its endogenous ligand via a cysteine-rich domain; however, the function of the equivalent domain in Smoothened, a mediator of Hedgehog signalling, is unknown. Rana et al.present the NMR solution structure of this domain, and characterize its interaction with the glucocorticoid budesonide.

    • Rajashree Rana
    • , Candace E. Carroll
    •  & Jie J. Zheng

  • Article
    | Open Access

    Levels of extracellular calcium can increase at sites of infection and inflammation; however, the physiological significance of this has been unclear. This work shows that extracellular calcium acts as a danger signal, triggering the NLRP3 inflammasome via two G protein-coupled receptors.

    • Manuela Rossol
    • , Matthias Pierer
    •  & Ulf Wagner

  • Article
    | Open Access

    Many drugs exist that target the β-adrenergic receptor, but they have different efficacies. Kofukuet al. use NMR to show that methionine 82 in the transmembrane domain undergoes conformational changes depending on whether agonists or inverse agonists are bound, explaining the differential drug efficacy.

    • Yutaka Kofuku
    • , Takumi Ueda
    •  & Ichio Shimada

  • Article
    | Open Access

    Following retinalcis/trans isomerisation, the active form of the G-protein-coupled receptor rhodopsin decays to opsin and all-trans-retinal. In this study, arrestin, a regulator of G-protein-coupled receptor activity, is shown to facilitate the concurrent sequestering of toxic all-trans-retinal and regeneration of 11-cis-retinal within the opsin population.

    • Martha E. Sommer
    • , Klaus Peter Hofmann
    •  & Martin Heck

  • Article
    | Open Access

    G-protein-coupled receptors sense extracellular cues and transmit the signal to distinct trimeric G-proteins. Stefanet al.show that in response to cAMP, a central and conserved component of the Gαs-coupled receptor cascade, the RII subunit of PKA, specifically binds to and participates in Gαi signaling.

    • Eduard Stefan
    • , Mohan K. Malleshaiah
    •  & Stephen W. Michnick

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