Extracellular signalling molecules articles within Nature Communications

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  • Article
    | Open Access

    The precise regulatory mechanisms controlling ciliary Hedgehog signaling remain incomplete. Here, the authors use ciliary proteomics to reveal that Numb facilitates the endocytosis of the receptor Ptch1 from the ciliary pocket, thereby enabling activation of Hedgehog signaling.

    • Xiaoliang Liu
    • , Patricia T. Yam
    •  & Xuecai Ge

  • Article
    | Open Access

    Whether Kupffer cells play a role in regulating the pathogenesis of fatty liver disease remains to be completely explored. Here, the authors show GPR3 activation stimulates glycolysis in Kupffer cells through GPR3-β-arrestin2-GAPDHPKM2 pathway and inhibits high-fat diet induced obesity and liver pathogenesis.

    • Ting Dong
    • , Guangan Hu
    •  & Jianzhu Chen

  • Article
    | Open Access

    A complex interplay of various backgrounds and conditions determines the body fat levels of individuals. Here, the authors identify HSP47 as a pivotal determinant of body adiposity which is abundantly expressed in fat tissue and influenced by factors such as diet, exercise, hormones, and genetics.

    • Jihoon Shin
    • , Shinichiro Toyoda
    •  & Iichiro Shimomura

  • Article
    | Open Access

    Generation of primordial germ cell-like cells (PGCLCs) from human pluripotent cells (hPSCs) offers insight into the mechanisms underlying human reproduction, but often requires complex methods. Here they describe a simplified monolayer protocol to differentiate and purify PGCLCs for further analysis.

    • Sivakamasundari Vijayakumar
    • , Roberta Sala
    •  & Vittorio Sebastiano

  • Article
    | Open Access

    Signals from extracellular cues orienting growing axons are thought to be integrated by second messenger molecules. Here, Baudet et al. instead demonstrate that distinct axon guidance cues induce cAMP, cGMP and Ca2+ signals restricted to separate cellular nanodomains.

    • Sarah Baudet
    • , Yvrick Zagar
    •  & Xavier Nicol

  • Article
    | Open Access

    Most intestinal organoid models do not accurately model the interactions between epithelial and stromal cells. Here they establish a colon assembloid system with epithelial and stromal cells and demonstrate that BMP signals from differentiating epithelial cells promote mesenchymal niche organization.

    • Manqiang Lin
    • , Kimberly Hartl
    •  & Michael Sigal

  • Article
    | Open Access

    The p140Cap adaptor protein is a tumour suppressor associated with improved prognosis in breast cancer. Here, the authors identify a role for p140Cap in preventing the immunosuppressive and pro-tumour function of polymorphonuclear myeloid-derived suppressor cells via downmodulation of the β-Catenin/Tumor Initiating Cells/G-CSF axi

    • Vincenzo Salemme
    • , Mauro Vedelago
    •  & Paola Defilippi

  • Article
    | Open Access

    The antigen-B-cell-receptor interaction is the driving force of terminal B cell development that spans from B cell activation to antibody secreting plasma cells. Here authors determine, using DNA-PAINT super-resolution microscopy, how antigen affinity and valency define antigen binding to BCR in an in vitro system allowing precision control of these parameters.

    • Alexey Ferapontov
    • , Marjan Omer
    •  & Søren Egedal Degn

  • Article
    | Open Access

    SVEP1 is linked to numerous human diseases, though its disease-promoting mechanism has remained unclear. Here, the authors identify SVEP1 as a ligand for the orphan receptor PEAR1 and provide insight into the role of this interaction in cardiovascular disease.

    • Jared S. Elenbaas
    • , Upasana Pudupakkam
    •  & Nathan O. Stitziel

  • Article
    | Open Access

    How carvedilol, a β1-blocker, activates β2-adrenoceptors, is unclear. Here, the authors resolve this enigma and show that carvedilol drives all of its detectable cellular β2-adrenoceptor signals by slow and low efficacy G protein activation.

    • Tobias Benkel
    • , Mirjam Zimmermann
    •  & Evi Kostenis

  • Article
    | Open Access

    Specificity in signaling activated by receptor tyrosine kinases is typically attributed to characteristics of their intracellular domains. Here, the authors demonstrate that an extracellular receptor sequence motif controls intracellular signaling as a result of extracellular glycan interactions.

    • Katri Vaparanta
    • , Anne Jokilammi
    •  & Klaus Elenius

  • Article
    | Open Access

    The epithelial protein Coxsackievirus Adenovirus Receptor (CAR) is a virus receptor but may have other functions. Here the authors show that deletion of CAR in mice leads to reduced house dust mite-induced lung inflammation, reduced neutrophil accumulation and alterations in airway remodelling.

    • Elena Ortiz-Zapater
    • , Dustin C. Bagley
    •  & Maddy Parsons

  • Article
    | Open Access

    G protein-coupled receptors (GPCRs) enable cells to sense environmental cues and are indispensable for coordinating vital processes including quorum sensing, proliferation, and sexual reproduction. Here the authors, using heterologous GPCR expression and endogenous ligand production, enable synthetic mating in haploid yeast, and GPCR-mediated biosensing in diploid probiotic yeast.

    • Emil D. Jensen
    • , Marcus Deichmann
    •  & Michael K. Jensen

  • Article
    | Open Access

    Lack of CD8+ T-cell infiltration into solid tumors is associated with poor responsiveness to immune checkpoint therapy (ICT). Here, the authors show that blocking the phosphorylation of HRS to reduce the induction of immunosuppressive exosomes promotes CD8+ T-cell infiltration into tumors and enhances the efficacy of ICT in mouse melanoma models.

    • Lei Guan
    • , Bin Wu
    •  & Wei Guo

  • Article
    | Open Access

    Picornaviruses can escape infected cells via packaging in extracellular vesicles (EVs). Here, van der Grein et al. show that the non-structural Leader protein of encephalomyocarditis virus (EMCV) promotes the release of EV-enclosed virus particles and provide evidence for a role of secretory autophagy in this process.

    • Susanne G. van der Grein
    • , Kyra A. Y. Defourny
    •  & Esther N. M. Nolte-‘t Hoen

  • Article
    | Open Access

    T cells communicate with antigen-presenting cells (APC) via the signaling crosstalk at the immunological synapse (IS). Here the authors use bead-supported lipid bilayers as synthetic APCs to find that trans-synaptic vesicles produced by T cells in the IS carry specialized cargos distinct from constitutive extracellular vesicles to serve as intercellular messengers.

    • Pablo F. Céspedes
    • , Ashwin Jainarayanan
    •  & Michael L. Dustin

  • Article
    | Open Access

    Cytonemes are signaling filopodia that mediate target-specific long-distance communications of signals like FGFs. Du et al. show that a Drosophila FGF is anchored to the FGF-producing cell surface, inhibiting free FGF secretion and activating contact-dependent bidirectional FGF-FGFR interactions, controlling target-specific cytoneme contacts and contact-dependent FGF release.

    • Lijuan Du
    • , Alex Sohr
    •  & Sougata Roy

  • Article
    | Open Access

    Intestinal stem cells contribute to homeostasis through a balance between self-renewal and differentiation. Here the authors show that CCN1 is an intestinal stem cell niche factor that activates integrin αvβ3/αvβ5 signaling to regulate proliferation and differentiation through distinct downstream pathways.

    • Jong Hoon Won
    • , Jacob S. Choi
    •  & Joon-Il Jun

  • Article
    | Open Access

    Interferon alpha (IFNalpha) therapy is showing promising results to treat myeloproliferative neoplasms (MPNs). Here, the authors show that IFNalpha response requires ULK1 phosphorylation to induce p38-MAPK signalling but it is counteracted by ROCK1-2 activation suggesting combination therapy of IFNalpha-ROCK1-2 inhibition may improve MPNs treatment.

    • Diana Saleiro
    • , Jeremy Q. Wen
    •  & Leonidas C. Platanias

  • Article
    | Open Access

    Mammary morphogenesis is a complex process. Here the authors describe how stem cells build a three-dimensional self-organizing multi-lineage tissue by showing that positional signals from the extracellular matrix through the collagen receptor DDR1 lead stem cells to differentiate into multi-lineage committed multi-layered progeny.

    • Gat Rauner
    • , Dexter X. Jin
    •  & Charlotte Kuperwasser

  • Article
    | Open Access

    Hedgehog-Interacting Protein (HHIP) is the only reported secreted inhibitor of Sonic Hedgehog (SHH) signalling. Here, the authors report structures of the HHIP N- and C-terminal domains, both in complexes with glycosaminoglycans, providing insights into the molecular basis for SHH sequestration and inhibition.

    • Samuel C. Griffiths
    • , Rebekka A. Schwab
    •  & Christian Siebold

  • Article
    | Open Access

    The spatial organization of cell surface receptors is critical for cell signaling and drug action. Here, the authors develop an optoproteomic method for mapping surface protein interactions, revealing cellular responses to antibodies, drugs and viral particles as well as immunosynapse signaling events.

    • Maik Müller
    • , Fabienne Gräbnitz
    •  & Bernd Wollscheid

  • Article
    | Open Access

    Notch receptor GLP-1 is required for maintaining germ cells in the C. elegans germline. Here the authors show that syndecan-1, a somatic transmembrane proteoglycan regulates expression of glp-1 and germ cell mitosis in C. elegans, by promoting calcium-dependent binding of APTF-2 to the glp-1 promoter.

    • Sandeep Gopal
    • , Aqilah Amran
    •  & Roger Pocock

  • Article
    | Open Access

    GAPDH is generally considered a housekeeping gene and functions in glycolysis. Here, the authors show that GAPDH has a role in promoting vesicle clustering in endosomes and can load siRNA onto the surface of extracellular vesicles, which can be exploited therapeutically.

    • Ghulam Hassan Dar
    • , Cláudia C. Mendes
    •  & Matthew J. A. Wood

  • Article
    | Open Access

    Proliferative and effector functions of T cells are determined by T cell receptor signalling and modulated by activator and inhibitory co-receptors. Authors report here that the G-protein-coupled receptor GPR171 functions as a co-inhibitor of T cell signalling and might serve as a target for cancer immunotherapy.

    • Yuki Fujiwara
    • , Robert J. Torphy
    •  & Yuwen Zhu

  • Article
    | Open Access

    Nonvesicular extracellular RNA (nex-RNA) that are not packed in extracellular vesicles is detected outside the cell, but it is poorly understood. Here the authors report that nex-RNA is captured by a zinc finger protein and transported to the nucleus to enhance antimetastatic characters of the cell.

    • Takeshi Tomita
    • , Masayoshi Kato
    •  & Sachie Hiratsuka

  • Article
    | Open Access

    The network of proteins secreted for interorgan communication is poorly understood. Here, the authors develop a method, based on protein labeling, to study cell-specific secretomes and interorgan protein trafficking, and demonstrate their approach in Drosophila and mouse models.

    • Ilia A. Droujinine
    • , Amanda S. Meyer
    •  & Norbert Perrimon

  • Article
    | Open Access

    Cytonemes are cellular projections known to transfer Wnt ligands between cells, but their regulation remains unclear. Here, the authors show that activation of the planar cell polarity protein Vangl2 generates long and branched cytonemes increasing paracrine Wnt/β-catenin signaling.

    • Lucy Brunt
    • , Gediminas Greicius
    •  & Steffen Scholpp

  • Article
    | Open Access

    Small molecules stabilising a distorted TNF trimer can inhibit TNF signaling, but the underlying mechanism is unclear. Here, the authors characterize the inhibitor-bound TNF-receptor complex structurally and biochemically, showing that the inhibitors alter TNF-receptor binding stoichiometry and cluster formation.

    • David McMillan
    • , Carlos Martinez-Fleites
    •  & James O’Connell

  • Article
    | Open Access

    The small molecule AI-2 acts as a quorum sensing signal, mediating communication within and between many bacterial species. Here, the authors identify a new type of AI-2 receptor, consisting of a dCACHE domain that is present in many bacterial and archaeal proteins.

    • Lei Zhang
    • , Shuyu Li
    •  & Xihui Shen

  • Article
    | Open Access

    The main site of cytokinin perception in plant cells is thought to be the endoplasmic reticulum where most cytokinin receptors localise. Here via the use of bioactive probes that cannot enter plant cells and super-resolution microscopy, Antoniadi et al. show that cytokinin can also be perceived at the plasma membrane.

    • Ioanna Antoniadi
    • , Ondřej Novák
    •  & Colin Turnbull

  • Article
    | Open Access

    Genetic variants at the RSPO3 locus are associated with waist-to-hip ratio (adjusted for BMI). Here, Loh et al. describe two independent RSPO3 signals that associate with body fat distribution, perform fine-mapping and explore the function of RSPO3 in human adipocyte biology and body fat distribution in zebrafish

    • Nellie Y. Loh
    • , James E. N. Minchin
    •  & Constantinos Christodoulides

  • Article
    | Open Access

    Epithelial gene expression has been shown to be zonated along the crypt-villus axis, but mechanisms shaping this spatial variability were unknown. Here, Bahar Halpern et al. uncover zonation of mesenchymal cells, including Lgr5+ telocytes, which regulate epithelial gene expression at the villus tip.

    • Keren Bahar Halpern
    • , Hassan Massalha
    •  & Shalev Itzkovitz

  • Article
    | Open Access

    Gram-positive bacteria can release signaling peptides that are ‘probed’ by intracellular receptors after being pumped into the cytoplasm. Here, Babel et al. show that these pump-probe networks can infer the fraction of signal-producing cells in a mixed population, and do not necessarily mediate typical quorum-sensing control.

    • Heiko Babel
    • , Pablo Naranjo-Meneses
    •  & Ilka B. Bischofs

  • Article
    | Open Access

    Extracellular vesicles (EVs) containing miRNAs or proteins can coordinate metabolic responses between tissues. Here the authors demonstrate that during lipid overload, the liver secretes miRNA-containing EVs through a Ggpps-Rab27 dependent mechanism, which controls adipose tissue lipid storage capacity.

    • Yue Zhao
    • , Meng-Fei Zhao
    •  & Chao-Jun Li

  • Article
    | Open Access

    Acetylcholine regulates intestinal epithelial secretion via muscarinic Gq-coupled receptors but its role in cell differentiation is unclear. Here, the authors show that Prox1-positive endocrine cells are sensors for the cholinergic intestinal niche and can trigger increased differentiation of enteroendocrine DCLK1-positive tuft cells.

    • Moritz Middelhoff
    • , Henrik Nienhüser
    •  & Timothy C. Wang

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