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GPCR activation and GRK2 assembly by a biased intracellular agonist
Structural studies on the complex containing G-protein-coupled receptor kinase 2 (GRK2), neurotensin receptor 1 (NTSR1), Gαq and the arrestin-biased ligand SBI-553 provide insights into these interactions and a foundation for the design of arrestin-biased ligands for G-protein-coupled receptors.
- Jia Duan
- , Heng Liu
- & H. Eric Xu
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Article
| Open AccessSignalling by senescent melanocytes hyperactivates hair growth
Senescent melanocytes of skin nevi drive hyperactivation of hair growth through the signalling factor SPP1.
- Xiaojie Wang
- , Raul Ramos
- & Maksim V. Plikus
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Molecular sensing of mechano- and ligand-dependent adhesion GPCR dissociation
A technique to detect the release of N-terminal fragments of Drosophila adhesion G-protein-coupled receptors (aGPCRs) provides insight into the dissociation of aGPCRs, and shows that receptor autoproteolysis enables non-cell-autonomous activity of aGPCRs in the brain.
- Nicole Scholz
- , Anne-Kristin Dahse
- & Tobias Langenhan
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Article
| Open AccessApoptotic brown adipocytes enhance energy expenditure via extracellular inosine
Untargeted metabolomics demonstrate that apoptotic brown adipocytes release a specific pattern of metabolites with purine metabolites being highly enriched, and inosine is identified as a metabolite released during apoptosis regulating thermogenic fat and counteracting obesity.
- Birte Niemann
- , Saskia Haufs-Brusberg
- & Alexander Pfeifer
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A hormone complex of FABP4 and nucleoside kinases regulates islet function
Hormonal FABP4 is discovered to be a pivotal regulator of an adipose–beta-cell endocrine axis that coordinates energy status and metabolic organ function, and targeting this axis improved metabolic outcomes.
- Kacey J. Prentice
- , Jani Saksi
- & Gökhan S. Hotamisligil
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Violet-light suppression of thermogenesis by opsin 5 hypothalamic neurons
Mice possess neurons in the preoptic area of the hypothalamus that are sensitive to violet light; these deep brain neurons sense light via OPN5 and regulate adaptive thermogenesis in brown fat.
- Kevin X. Zhang
- , Shane D’Souza
- & Richard A. Lang
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FERONIA controls pectin- and nitric oxide-mediated male–female interaction
FERONIA prevents polyspermy in Arabidopsis by enabling pectin-stimulated nitric oxide accumulation at the filiform apparatus after the first pollen tube arrives, which disengages LURE1 chemoattraction to prevent late-arriving pollen tubes from entering the ovule.
- Qiaohong Duan
- , Ming-Che James Liu
- & Alice Y. Cheung
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Hydrogen peroxide sensor HPCA1 is an LRR receptor kinase in Arabidopsis
HPCA1, a member of a previously uncharacterized subfamily of leucine-rich-repeat receptor-like kinases, is the hydrogen-peroxide sensor at the plasma membrane in Arabidopsis.
- Feihua Wu
- , Yuan Chi
- & Zhen-Ming Pei
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Letter |
Mechanosignalling via integrins directs fate decisions of pancreatic progenitors
Single-cell analysis reveals that interactions with the extracellular matrix via integrin α5 and mechanotransducer YAP1 determine whether pancreatic progenitors develop along the duct or endocrine lineages.
- Anant Mamidi
- , Christy Prawiro
- & Henrik Semb
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Coupling of bone resorption and formation by RANKL reverse signalling
Osteoclasts secrete small extracellular vesicles that stimulate osteoblasts, promoting bone formation via receptor activator of nuclear factor-kappa B ligand (RANKL), thereby linking bone formation and resorption.
- Yuki Ikebuchi
- , Shigeki Aoki
- & Hiroshi Suzuki
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Letter |
Structures of human Patched and its complex with native palmitoylated sonic hedgehog
High-resolution structures of the human plasma membrane protein patched 1 alone and in complex with the native form of the ligand sonic hedgehog are determined.
- Xiaofeng Qi
- , Philip Schmiege
- & Xiaochun Li
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Letter |
GLI1-expressing mesenchymal cells form the essential Wnt-secreting niche for colon stem cells
GLI1-positive cells in the colon secrete Wnt ligands and thereby support homeostasis of intestinal stem cells.
- Bahar Degirmenci
- , Tomas Valenta
- & Konrad Basler
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Letter |
The SMAD2/3 interactome reveals that TGFβ controls m6A mRNA methylation in pluripotency
The SMAD2 and SMAD3 protein interactome links TGFβ signalling to diverse effectors including m6A methyltransferase, which has a role in regulating differentiation of human pluripotent stem cells.
- Alessandro Bertero
- , Stephanie Brown
- & Ludovic Vallier
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Letter |
IL-11 is a crucial determinant of cardiovascular fibrosis
Fibroblast-specific Il-11 expression causes heart and kidney fibrosis and organ failure, whereas IL-11 inhibition prevents fibroblast activation and organ fibrosis, indicating that IL-11 inhibition is a potential therapeutic strategy to treat fibrotic diseases.
- Sebastian Schafer
- , Sivakumar Viswanathan
- & Stuart A. Cook
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Notum deacylates Wnt proteins to suppress signalling activity
The biochemical activity of Notum as a carboxylesterase that removes an essential lipid moiety from Wnt proteins is uncovered; the interaction of Notum with glypicans is required to ensure localization at the cell surface, and Notum may provide a new target for therapeutic development in diseases with defective Wnt signalling.
- Satoshi Kakugawa
- , Paul F. Langton
- & Jean-Paul Vincent
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Letter |
Luminal signalling links cell communication to tissue architecture during organogenesis
Groups of cells within a migrating collective assemble shared luminal cavities that trap and concentrate the signalling molecule fibroblast growth factor, providing a self-organising mechanism to focus and coordinate cell communication within tissues.
- Sevi Durdu
- , Murat Iskar
- & Darren Gilmour
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Letter |
Carbonic anhydrases, EPF2 and a novel protease mediate CO2 control of stomatal development
The continuing rise in atmospheric carbon dioxide concentrations suppresses the development of stomatal pores, and thus gas exchange, in plant leaves on a global scale; now, a framework of mechanisms by which carbon dioxide represses development has been identified.
- Cawas B. Engineer
- , Majid Ghassemian
- & Julian I. Schroeder
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CRTC3 links catecholamine signalling to energy balance
β-adrenergic receptor signalling in adipocytes stimulates energy expenditure via cAMP-dependent increases in lipolysis and fatty-acid oxidation, and this signalling mechanism is thought to be disrupted in obesity. Here, the cAMP-responsive CREB coactivator Crtc3 is shown to promote obesity in mice by attenuating β adrenergic receptor signalling in adipose tissue.
- Youngsup Song
- , Judith Altarejos
- & Marc Montminy