LynA regulates an inflammation-sensitive signaling checkpoint in macrophages.


:Clustering of receptors associated with immunoreceptor tyrosine-based activation motifs (ITAMs) initiates the macrophage antimicrobial response. ITAM receptors engage Src-family tyrosine kinases (SFKs) to initiate phagocytosis and macrophage activation. Macrophages also encounter nonpathogenic molecules that cluster receptors weakly and must tune their sensitivity to avoid inappropriate responses. To investigate this response threshold, we compared signaling in the presence and absence of receptor clustering using a small-molecule inhibitor of Csk, which increased SFK activation and produced robust membrane-proximal signaling. Surprisingly, receptor-independent SFK activation led to a downstream signaling blockade associated with rapid degradation of the SFK LynA. Inflammatory priming of macrophages upregulated LynA and promoted receptor-independent signaling. In contrast, clustering the hemi-ITAM receptor Dectin-1 induced signaling that did not require LynA or inflammatory priming. Together, the basal-state signaling checkpoint regulated by LynA expression and degradation and the signaling reorganization initiated by receptor clustering allow cells to discriminate optimally between pathogens and nonpathogens.






Freedman TS,Tan YX,Skrzypczynska KM,Manz BN,Sjaastad FV,Goodridge HS,Lowell CA,Weiss A




Has Abstract


2015-10-30 00:00:00








  • Voltage-dependent dynamics of the BK channel cytosolic gating ring are coupled to the membrane-embedded voltage sensor.

    abstract::In humans, large conductance voltage- and calcium-dependent potassium (BK) channels are regulated allosterically by transmembrane voltage and intracellular Ca2+. Divalent cation binding sites reside within the gating ring formed by two Regulator of Conductance of Potassium (RCK) domains per subunit. Using patch-clamp ...


    pub_type: 杂志文章


    authors: Miranda P,Holmgren M,Giraldez T

    更新日期:2018-12-11 00:00:00

  • Active and water-soluble form of lipidated Wnt protein is maintained by a serum glycoprotein afamin/α-albumin.

    abstract::Wnt plays important role during development and in various diseases. Because Wnts are lipidated and highly hydrophobic, they can only be purified in the presence of detergents, limiting their use in various in vitro and in vivo assays. We purified N-terminally tagged recombinant Wnt3a secreted from cells and accidenta...


    pub_type: 杂志文章


    authors: Mihara E,Hirai H,Yamamoto H,Tamura-Kawakami K,Matano M,Kikuchi A,Sato T,Takagi J

    更新日期:2016-02-23 00:00:00

  • A larger target leads to faster evolution.

    abstract::The speed at which a cell fate decision in nematode worms evolves is due to the number of genes that control the decision, rather than to a high mutation rate. ...


    pub_type: 评论,杂志文章


    authors: Yang B,Rifkin SA

    更新日期:2020-10-14 00:00:00

  • How lamina-associated polypeptide 1 (LAP1) activates Torsin.

    abstract::Lamina-associated polypeptide 1 (LAP1) resides at the nuclear envelope and interacts with Torsins, poorly understood endoplasmic reticulum (ER)-localized AAA+ ATPases, through a conserved, perinuclear domain. We determined the crystal structure of the perinuclear domain of human LAP1. LAP1 possesses an atypical AAA+ f...


    pub_type: 杂志文章


    authors: Sosa BA,Demircioglu FE,Chen JZ,Ingram J,Ploegh HL,Schwartz TU

    更新日期:2014-08-22 00:00:00

  • FBXL19 recruits CDK-Mediator to CpG islands of developmental genes priming them for activation during lineage commitment.

    abstract::CpG islands are gene regulatory elements associated with the majority of mammalian promoters, yet how they regulate gene expression remains poorly understood. Here, we identify FBXL19 as a CpG island-binding protein in mouse embryonic stem (ES) cells and show that it associates with the CDK-Mediator complex. We discov...


    pub_type: 杂志文章


    authors: Dimitrova E,Kondo T,Feldmann A,Nakayama M,Koseki Y,Konietzny R,Kessler BM,Koseki H,Klose RJ

    更新日期:2018-05-29 00:00:00

  • How biological attention mechanisms improve task performance in a large-scale visual system model.

    abstract::How does attentional modulation of neural activity enhance performance? Here we use a deep convolutional neural network as a large-scale model of the visual system to address this question. We model the feature similarity gain model of attention, in which attentional modulation is applied according to neural stimulus ...


    pub_type: 杂志文章


    authors: Lindsay GW,Miller KD

    更新日期:2018-10-01 00:00:00

  • KIF2A regulates the development of dentate granule cells and postnatal hippocampal wiring.

    abstract::Kinesin super family protein 2A (KIF2A), an ATP-dependent microtubule (MT) destabilizer, regulates cell migration, axon elongation, and pruning in the developing nervous system. KIF2A mutations have recently been identified in patients with malformed cortical development. However, postnatal KIF2A is continuously expre...


    pub_type: 杂志文章


    authors: Homma N,Zhou R,Naseer MI,Chaudhary AG,Al-Qahtani MH,Hirokawa N

    更新日期:2018-01-09 00:00:00

  • Integrated externally and internally generated task predictions jointly guide cognitive control in prefrontal cortex.

    abstract::Cognitive control proactively configures information processing to suit expected task demands. Predictions of forthcoming demand can be driven by explicit external cues or be generated internally, based on past experience (cognitive history). However, it is not known whether and how the brain reconciles these two sour...


    pub_type: 杂志文章


    authors: Jiang J,Wagner AD,Egner T

    更新日期:2018-08-16 00:00:00

  • Dopamine receptor 1 neurons in the dorsal striatum regulate food anticipatory circadian activity rhythms in mice.

    abstract::Daily rhythms of food anticipatory activity (FAA) are regulated independently of the suprachiasmatic nucleus, which mediates entrainment of rhythms to light, but the neural circuits that establish FAA remain elusive. In this study, we show that mice lacking the dopamine D1 receptor (D1R KO mice) manifest greatly reduc...


    pub_type: 杂志文章


    authors: Gallardo CM,Darvas M,Oviatt M,Chang CH,Michalik M,Huddy TF,Meyer EE,Shuster SA,Aguayo A,Hill EM,Kiani K,Ikpeazu J,Martinez JS,Purpura M,Smit AN,Patton DF,Mistlberger RE,Palmiter RD,Steele AD

    更新日期:2014-09-12 00:00:00

  • Orbitofrontal neurons signal sensory associations underlying model-based inference in a sensory preconditioning task.

    abstract::Using knowledge of the structure of the world to infer value is at the heart of model-based reasoning and relies on a circuit that includes the orbitofrontal cortex (OFC). Some accounts link this to the representation of biological significance or value by neurons in OFC, while other models focus on the representation...


    pub_type: 杂志文章


    authors: Sadacca BF,Wied HM,Lopatina N,Saini GK,Nemirovsky D,Schoenbaum G

    更新日期:2018-03-07 00:00:00

  • Human biallelic MFN2 mutations induce mitochondrial dysfunction, upper body adipose hyperplasia, and suppression of leptin expression.

    abstract::MFN2 encodes mitofusin 2, a membrane-bound mediator of mitochondrial membrane fusion and inter-organelle communication. MFN2 mutations cause axonal neuropathy, with associated lipodystrophy only occasionally noted, however homozygosity for the p.Arg707Trp mutation was recently associated with upper body adipose overgr...


    pub_type: 杂志文章


    authors: Rocha N,Bulger DA,Frontini A,Titheradge H,Gribsholt SB,Knox R,Page M,Harris J,Payne F,Adams C,Sleigh A,Crawford J,Gjesing AP,Bork-Jensen J,Pedersen O,Barroso I,Hansen T,Cox H,Reilly M,Rossor A,Brown RJ,Taylor SI

    更新日期:2017-04-19 00:00:00

  • Kinesin and dynein use distinct mechanisms to bypass obstacles.

    abstract::Kinesin-1 and cytoplasmic dynein are microtubule (MT) motors that transport intracellular cargoes. It remains unclear how these motors move along MTs densely coated with obstacles of various sizes in the cytoplasm. Here, we tested the ability of single and multiple motors to bypass synthetic obstacles on MTs in vitro....


    pub_type: 杂志文章


    authors: Ferro LS,Can S,Turner MA,ElShenawy MM,Yildiz A

    更新日期:2019-09-09 00:00:00

  • Cracking Ali Baba's code.

    abstract::A protein called P36 holds the key to how different species of malaria parasite invade liver cells. ...


    pub_type: 评论,杂志文章


    authors: Billker O

    更新日期:2017-06-14 00:00:00

  • Pervasive duplication of tumor suppressors in Afrotherians during the evolution of large bodies and reduced cancer risk.

    abstract::The risk of developing cancer is correlated with body size and lifespan within species. Between species, however, there is no correlation between cancer and either body size or lifespan, indicating that large, long-lived species have evolved enhanced cancer protection mechanisms. Elephants and their relatives (Probosc...


    pub_type: 杂志文章


    authors: Vazquez JM,Lynch VJ

    更新日期:2021-01-29 00:00:00

  • The circuitry of sex.

    abstract::Neural circuits that control copulation in male flies have been identified. ...


    pub_type: 评论,杂志文章


    authors: Levine J

    更新日期:2016-11-15 00:00:00

  • The yellow gene influences Drosophila male mating success through sex comb melanization.

    abstract::Drosophila melanogaster males perform a series of courtship behaviors that, when successful, result in copulation with a female. For over a century, mutations in the yellow gene, named for its effects on pigmentation, have been known to reduce male mating success. Prior work has suggested that yellow influences mating...


    pub_type: 杂志文章


    authors: Massey JH,Chung D,Siwanowicz I,Stern DL,Wittkopp PJ

    更新日期:2019-10-15 00:00:00

  • FAK activity sustains intrinsic and acquired ovarian cancer resistance to platinum chemotherapy.

    abstract::Gene copy number alterations, tumor cell stemness, and the development of platinum chemotherapy resistance contribute to high-grade serous ovarian cancer (HGSOC) recurrence. Stem phenotypes involving Wnt-β-catenin, aldehyde dehydrogenase activities, intrinsic platinum resistance, and tumorsphere formation are here ass...


    pub_type: 杂志文章


    authors: Diaz Osterman CJ,Ozmadenci D,Kleinschmidt EG,Taylor KN,Barrie AM,Jiang S,Bean LM,Sulzmaier FJ,Jean C,Tancioni I,Anderson K,Uryu S,Cordasco EA,Li J,Chen XL,Fu G,Ojalill M,Rappu P,Heino J,Mark AM,Xu G,Fisch KM,K

    更新日期:2019-09-03 00:00:00

  • Effects of microcompartmentation on flux distribution and metabolic pools in Chlamydomonas reinhardtii chloroplasts.

    abstract::Cells and organelles are not homogeneous but include microcompartments that alter the spatiotemporal characteristics of cellular processes. The effects of microcompartmentation on metabolic pathways are however difficult to study experimentally. The pyrenoid is a microcompartment that is essential for a carbon concent...


    pub_type: 杂志文章


    authors: Küken A,Sommer F,Yaneva-Roder L,Mackinder LC,Höhne M,Geimer S,Jonikas MC,Schroda M,Stitt M,Nikoloski Z,Mettler-Altmann T

    更新日期:2018-10-11 00:00:00

  • Localized epigenetic silencing of a damage-activated WNT enhancer limits regeneration in mature Drosophila imaginal discs.

    abstract::Many organisms lose the capacity to regenerate damaged tissues as they mature. Damaged Drosophila imaginal discs regenerate efficiently early in the third larval instar (L3) but progressively lose this ability. This correlates with reduced damage-responsive expression of multiple genes, including the WNT genes wingles...


    pub_type: 杂志文章


    authors: Harris RE,Setiawan L,Saul J,Hariharan IK

    更新日期:2016-02-03 00:00:00

  • Ten simple rules for the computational modeling of behavioral data.

    abstract::Computational modeling of behavior has revolutionized psychology and neuroscience. By fitting models to experimental data we can probe the algorithms underlying behavior, find neural correlates of computational variables and better understand the effects of drugs, illness and interventions. But with great power comes ...


    pub_type: 杂志文章


    authors: Wilson RC,Collins AG

    更新日期:2019-11-26 00:00:00

  • The Ndc80 complex bridges two Dam1 complex rings.

    abstract::Strong kinetochore-microtubule attachments are essential for faithful segregation of sister chromatids during mitosis. The Dam1 and Ndc80 complexes are the main microtubule binding components of the Saccharomyces cerevisiae kinetochore. Cooperation between these two complexes enhances kinetochore-microtubule coupling ...


    pub_type: 杂志文章


    authors: Kim JO,Zelter A,Umbreit NT,Bollozos A,Riffle M,Johnson R,MacCoss MJ,Asbury CL,Davis TN

    更新日期:2017-02-13 00:00:00

  • Vicarious reward unblocks associative learning about novel cues in male rats.

    abstract::Many species, including rats, are sensitive to social signals and their valuation is important in social learning. Here we introduce a task that investigates if mutual reward delivery in male rats can drive associative learning. We found that when actor rats have fully learned a stimulus-self-reward association, addin...


    pub_type: 杂志文章


    authors: van Gurp S,Hoog J,Kalenscher T,van Wingerden M

    更新日期:2020-10-01 00:00:00

  • 5-HT2a receptor in mPFC influences context-guided reconsolidation of object memory in perirhinal cortex.

    abstract::Context-dependent memories may guide adaptive behavior relaying in previous experience while updating stored information through reconsolidation. Retrieval can be triggered by partial and shared cues. When the cue is presented, the most relevant memory should be updated. In a contextual version of the object recogniti...


    pub_type: 杂志文章


    authors: Morici JF,Miranda M,Gallo FT,Zanoni B,Bekinschtein P,Weisstaub NV

    更新日期:2018-05-02 00:00:00

  • Decoding WW domain tandem-mediated target recognitions in tissue growth and cell polarity.

    abstract::WW domain tandem-containing proteins such as KIBRA, YAP, and MAGI play critical roles in cell growth and polarity via binding to and positioning target proteins in specific subcellular regions. An immense disparity exists between promiscuity of WW domain-mediated target bindings and specific roles of WW domain protein...


    pub_type: 杂志文章


    authors: Lin Z,Yang Z,Xie R,Ji Z,Guan K,Zhang M

    更新日期:2019-09-05 00:00:00

  • Mechanisms that allow cortical preparatory activity without inappropriate movement.

    abstract::We reveal a novel mechanism that explains how preparatory activity can evolve in motor-related cortical areas without prematurely inducing movement. The smooth eye movement region of the frontal eye fields (FEFSEM) is a critical node in the neural circuit controlling smooth pursuit eye movement. Preparatory activity e...


    pub_type: 杂志文章


    authors: Darlington TR,Lisberger SG

    更新日期:2020-02-21 00:00:00

  • The age of Homo naledi and associated sediments in the Rising Star Cave, South Africa.

    abstract::New ages for flowstone, sediments and fossil bones from the Dinaledi Chamber are presented. We combined optically stimulated luminescence dating of sediments with U-Th and palaeomagnetic analyses of flowstones to establish that all sediments containing Homo naledi fossils can be allocated to a single stratigraphic ent...


    pub_type: 杂志文章


    authors: Dirks PH,Roberts EM,Hilbert-Wolf H,Kramers JD,Hawks J,Dosseto A,Duval M,Elliott M,Evans M,Grün R,Hellstrom J,Herries AI,Joannes-Boyau R,Makhubela TV,Placzek CJ,Robbins J,Spandler C,Wiersma J,Woodhead J,Berger LR

    更新日期:2017-05-09 00:00:00

  • Akt regulation of glycolysis mediates bioenergetic stability in epithelial cells.

    abstract::Cells use multiple feedback controls to regulate metabolism in response to nutrient and signaling inputs. However, feedback creates the potential for unstable network responses. We examined how concentrations of key metabolites and signaling pathways interact to maintain homeostasis in proliferating human cells, using...


    pub_type: 杂志文章


    authors: Hung YP,Teragawa C,Kosaisawe N,Gillies TE,Pargett M,Minguet M,Distor K,Rocha-Gregg BL,Coloff JL,Keibler MA,Stephanopoulos G,Yellen G,Brugge JS,Albeck JG

    更新日期:2017-12-14 00:00:00

  • Small conductance Ca2+-activated K+ channels induce the firing pause periods during the activation of Drosophila nociceptive neurons.

    abstract::In Drosophila larvae, Class IV sensory neurons respond to noxious thermal stimuli and provoke heat avoidance behavior. Previously, we showed that the activated neurons displayed characteristic fluctuations of firing rates, which consisted of repetitive high-frequency spike trains and subsequent pause periods, and we p...


    pub_type: 杂志文章


    authors: Onodera K,Baba S,Murakami A,Uemura T,Usui T

    更新日期:2017-10-16 00:00:00

  • Critical role of WNK1 in MYC-dependent early mouse thymocyte development.

    abstract::WNK1, a kinase that controls kidney salt homeostasis, also regulates adhesion and migration in CD4+ T cells. Wnk1 is highly expressed in thymocytes, and since migration is important for thymocyte maturation, we investigated a role for WNK1 in mouse thymocyte development. We find that WNK1 is required for the transitio...


    pub_type: 杂志文章


    authors: Köchl R,Vanes L,Llorian Sopena M,Chakravarty P,Hartweger H,Fountain K,White A,Cowan J,Anderson G,Tybulewicz VL

    更新日期:2020-10-14 00:00:00

  • Plasmodium P36 determines host cell receptor usage during sporozoite invasion.

    abstract::Plasmodium sporozoites, the mosquito-transmitted forms of the malaria parasite, first infect the liver for an initial round of replication before the emergence of pathogenic blood stages. Sporozoites represent attractive targets for antimalarial preventive strategies, yet the mechanisms of parasite entry into hepatocy...


    pub_type: 杂志文章


    authors: Manzoni G,Marinach C,Topçu S,Briquet S,Grand M,Tolle M,Gransagne M,Lescar J,Andolina C,Franetich JF,Zeisel MB,Huby T,Rubinstein E,Snounou G,Mazier D,Nosten F,Baumert TF,Silvie O

    更新日期:2017-05-16 00:00:00