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








  • Gdf3 is required for robust Nodal signaling during germ layer formation and left-right patterning.

    abstract::Vertebrate embryonic patterning depends on signaling from Nodal, a TGFβ superfamily member. There are three Nodal orthologs in zebrafish; southpaw directs left-right asymmetries, while squint and cyclops function earlier to pattern mesendoderm. TGFβ member Vg1 is implicated in mesoderm formation but the role of the ze...


    pub_type: 杂志文章


    authors: Pelliccia JL,Jindal GA,Burdine RD

    更新日期:2017-11-15 00:00:00

  • Endosomal Rab cycles regulate Parkin-mediated mitophagy.

    abstract::Damaged mitochondria are selectively eliminated by mitophagy. Parkin and PINK1, gene products mutated in familial Parkinson's disease, play essential roles in mitophagy through ubiquitination of mitochondria. Cargo ubiquitination by E3 ubiquitin ligase Parkin is important to trigger selective autophagy. Although autop...


    pub_type: 杂志文章


    authors: Yamano K,Wang C,Sarraf SA,Münch C,Kikuchi R,Noda NN,Hizukuri Y,Kanemaki MT,Harper W,Tanaka K,Matsuda N,Youle RJ

    更新日期:2018-01-23 00:00:00

  • De-repression of the RAC activator ELMO1 in cancer stem cells drives progression of TGFβ-deficient squamous cell carcinoma from transition zones.

    abstract::Squamous cell carcinomas occurring at transition zones are highly malignant tumors with poor prognosis. The identity of the cell population and the signaling pathways involved in the progression of transition zone squamous cell carcinoma are poorly understood, hence representing limited options for targeted therapies....


    pub_type: 杂志文章


    authors: McCauley HA,Chevrier V,Birnbaum D,Guasch G

    更新日期:2017-02-21 00:00:00

  • High-throughput synapse-resolving two-photon fluorescence microendoscopy for deep-brain volumetric imaging in vivo.

    abstract::Optical imaging has become a powerful tool for studying brains in vivo. The opacity of adult brains makes microendoscopy, with an optical probe such as a gradient index (GRIN) lens embedded into brain tissue to provide optical relay, the method of choice for imaging neurons and neural activity in deeply buried brain s...


    pub_type: 杂志文章


    authors: Meng G,Liang Y,Sarsfield S,Jiang WC,Lu R,Dudman JT,Aponte Y,Ji N

    更新日期:2019-01-04 00:00:00

  • Slo2 potassium channel function depends on RNA editing-regulated expression of a SCYL1 protein.

    abstract::Slo2 potassium channels play important roles in neuronal function, and their mutations in humans may cause epilepsies and cognitive defects. However, it is largely unknown how Slo2 is regulated by other proteins. Here we show that the function of C. elegans Slo2 (SLO-2) depends on adr-1, a gene important to RNA editin...


    pub_type: 杂志文章


    authors: Niu LG,Liu P,Wang ZW,Chen B

    更新日期:2020-04-21 00:00:00

  • Position- and Hippo signaling-dependent plasticity during lineage segregation in the early mouse embryo.

    abstract::The segregation of the trophectoderm (TE) from the inner cell mass (ICM) in the mouse blastocyst is determined by position-dependent Hippo signaling. However, the window of responsiveness to Hippo signaling, the exact timing of lineage commitment and the overall relationship between cell commitment and global gene exp...


    pub_type: 杂志文章


    authors: Posfai E,Petropoulos S,de Barros FRO,Schell JP,Jurisica I,Sandberg R,Lanner F,Rossant J

    更新日期:2017-02-22 00:00:00

  • FlpStop, a tool for conditional gene control in Drosophila.

    abstract::Manipulating gene function cell type-specifically is a common experimental goal in Drosophila research and has been central to studies of neural development, circuit computation, and behavior. However, current cell type-specific gene disruption techniques in flies often reduce gene activity incompletely or rely on cel...


    pub_type: 杂志文章


    authors: Fisher YE,Yang HH,Isaacman-Beck J,Xie M,Gohl DM,Clandinin TR

    更新日期:2017-02-17 00:00:00

  • The structure of the Ctf19c/CCAN from budding yeast.

    abstract::Eukaryotic kinetochores connect spindlemicrotubules to chromosomal centromeres. A group of proteins called the Ctf19 complex (Ctf19c) in yeast and the constitutive centromere associated network (CCAN) in other organisms creates the foundation of a kinetochore. The Ctf19c/CCAN influences the timing of kinetochore assem...


    pub_type: 杂志文章


    authors: Hinshaw SM,Harrison SC

    更新日期:2019-02-14 00:00:00

  • Insulin signaling controls neurotransmission via the 4eBP-dependent modification of the exocytotic machinery.

    abstract::Altered insulin signaling has been linked to widespread nervous system dysfunction including cognitive dysfunction, neuropathy and susceptibility to neurodegenerative disease. However, knowledge of the cellular mechanisms underlying the effects of insulin on neuronal function is incomplete. Here, we show that cell aut...


    pub_type: 杂志文章


    authors: Mahoney RE,Azpurua J,Eaton BA

    更新日期:2016-08-15 00:00:00

  • Distinct contributions of the thin and thick filaments to length-dependent activation in heart muscle.

    abstract::The Frank-Starling relation is a fundamental auto-regulatory property of the heart that ensures the volume of blood ejected in each heartbeat is matched to the extent of venous filling. At the cellular level, heart muscle cells generate higher force when stretched, but despite intense efforts the underlying molecular ...


    pub_type: 杂志文章


    authors: Zhang X,Kampourakis T,Yan Z,Sevrieva I,Irving M,Sun YB

    更新日期:2017-02-23 00:00:00

  • Different dendritic domains of the GnRH neuron underlie the pulse and surge modes of GnRH secretion in female mice.

    abstract::The gonadotropin-releasing hormone (GnRH) neurons exhibit pulse and surge modes of activity to control fertility. They also exhibit an unusual bipolar morphology comprised of a classical soma-proximal dendritic zone and an elongated secretory process that can operate as both a dendrite and an axon, termed a 'dendron'....


    pub_type: 杂志文章


    authors: Wang L,Guo W,Shen X,Yeo S,Long H,Wang Z,Lyu Q,Herbison AE,Kuang Y

    更新日期:2020-07-09 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

  • Retinal stem cells modulate proliferative parameters to coordinate post-embryonic morphogenesis in the eye of fish.

    abstract::Combining clonal analysis with a computational agent based model, we investigate how tissue-specific stem cells for neural retina (NR) and retinal pigmented epithelium (RPE) of the teleost medaka (Oryzias latipes) coordinate their growth rates. NR cell division timing is less variable, consistent with an upstream role...


    pub_type: 杂志文章


    authors: Tsingos E,Höckendorf B,Sütterlin T,Kirchmaier S,Grabe N,Centanin L,Wittbrodt J

    更新日期:2019-03-26 00:00:00

  • Differential effects of light and feeding on circadian organization of peripheral clocks in a forebrain Bmal1 mutant.

    abstract::In order to assess the contribution of a central clock in the hypothalamic suprachiasmatic nucleus (SCN) to circadian behavior and the organization of peripheral clocks, we generated forebrain/SCN-specific Bmal1 knockout mice by using floxed Bmal1 and pan-neuronal Cre lines. The forebrain knockout mice showed >90% del...


    pub_type: 杂志文章


    authors: Izumo M,Pejchal M,Schook AC,Lange RP,Walisser JA,Sato TR,Wang X,Bradfield CA,Takahashi JS

    更新日期:2014-12-19 00:00:00

  • A retrospective analysis of the peer review of more than 75,000 Marie Curie proposals between 2007 and 2018.

    abstract::Most funding agencies rely on peer review to evaluate grant applications and proposals, but research into the use of this process by funding agencies has been limited. Here we explore if two changes to the organization of peer review for proposals submitted to various funding actions by the European Union has an influ...


    pub_type: 杂志文章


    authors: Pina DG,Buljan I,Hren D,Marušić A

    更新日期:2021-01-13 00:00:00

  • bicoid mRNA localises to the Drosophila oocyte anterior by random Dynein-mediated transport and anchoring.

    abstract::bicoid mRNA localises to the Drosophila oocyte anterior from stage 9 of oogenesis onwards to provide a local source for Bicoid protein for embryonic patterning. Live imaging at stage 9 reveals that bicoid mRNA particles undergo rapid Dynein-dependent movements near the oocyte anterior, but with no directional bias. Fu...


    pub_type: 杂志文章


    authors: Trovisco V,Belaya K,Nashchekin D,Irion U,Sirinakis G,Butler R,Lee JJ,Gavis ER,St Johnston D

    更新日期:2016-10-28 00:00:00

  • Alterations in the amplitude and burst rate of beta oscillations impair reward-dependent motor learning in anxiety.

    abstract::Anxiety results in sub-optimal motor learning, but the precise mechanisms through which this effect occurs remain unknown. Using a motor sequence learning paradigm with separate phases for initial exploration and reward-based learning, we show that anxiety states in humans impair learning by attenuating the update of ...


    pub_type: 杂志文章


    authors: Sporn S,Hein T,Herrojo Ruiz M

    更新日期:2020-05-19 00:00:00

  • CHIP as a membrane-shuttling proteostasis sensor.

    abstract::Cells respond to protein misfolding and aggregation in the cytosol by adjusting gene transcription and a number of post-transcriptional processes. In parallel to functional reactions, cellular structure changes as well; however, the mechanisms underlying the early adaptation of cellular compartments to cytosolic prote...


    pub_type: 杂志文章


    authors: Kopp Y,Lang WH,Schuster TB,Martínez-Limón A,Hofbauer HF,Ernst R,Calloni G,Vabulas RM

    更新日期:2017-11-01 00:00:00

  • Step-to-step variations in human running reveal how humans run without falling.

    abstract::Humans can run without falling down, usually despite uneven terrain or occasional pushes. Even without such external perturbations, intrinsic sources like sensorimotor noise perturb the running motion incessantly, making each step variable. Here, using simple and generalizable models, we show that even such small step...


    pub_type: 杂志文章


    authors: Seethapathi N,Srinivasan M

    更新日期:2019-03-19 00:00:00

  • Pervasive transcription read-through promotes aberrant expression of oncogenes and RNA chimeras in renal carcinoma.

    abstract::Aberrant expression of cancer genes and non-canonical RNA species is a hallmark of cancer. However, the mechanisms driving such atypical gene expression programs are incompletely understood. Here, our transcriptional profiling of a cohort of 50 primary clear cell renal cell carcinoma (ccRCC) samples from The Cancer Ge...


    pub_type: 杂志文章


    authors: Grosso AR,Leite AP,Carvalho S,Matos MR,Martins FB,Vítor AC,Desterro JM,Carmo-Fonseca M,de Almeida SF

    更新日期:2015-11-17 00:00:00

  • Time- and polarity-dependent proteomic changes associated with homeostatic scaling at central synapses.

    abstract::In homeostatic scaling at central synapses, the depth and breadth of cellular mechanisms that detect the offset from the set-point, detect the duration of the offset and implement a cellular response are not well understood. To understand the time-dependent scaling dynamics we treated cultured rat hippocampal cells wi...


    pub_type: 杂志文章


    authors: Schanzenbächer CT,Langer JD,Schuman EM

    更新日期:2018-02-15 00:00:00

  • The benefits of treating undetectable tumors.

    abstract::Cancer prevention is predicted to result in more positive therapeutic outcomes than post-diagnostic interventions, and so may be a viable option for future personalized medicine. ...


    pub_type: 评论,杂志文章


    authors: Komarova NL

    更新日期:2015-08-05 00:00:00

  • Hypothalamic transcriptomes of 99 mouse strains reveal trans eQTL hotspots, splicing QTLs and novel non-coding genes.

    abstract::Previous studies had shown that the integration of genome wide expression profiles, in metabolic tissues, with genetic and phenotypic variance, provided valuable insight into the underlying molecular mechanisms. We used RNA-Seq to characterize hypothalamic transcriptome in 99 inbred strains of mice from the Hybrid Mou...


    pub_type: 杂志文章


    authors: Hasin-Brumshtein Y,Khan AH,Hormozdiari F,Pan C,Parks BW,Petyuk VA,Piehowski PD,Brümmer A,Pellegrini M,Xiao X,Eskin E,Smith RD,Lusis AJ,Smith DJ

    更新日期:2016-09-13 00:00:00

  • Population scale mapping of transposable element diversity reveals links to gene regulation and epigenomic variation.

    abstract::Variation in the presence or absence of transposable elements (TEs) is a major source of genetic variation between individuals. Here, we identified 23,095 TE presence/absence variants between 216 Arabidopsis accessions. Most TE variants were rare, and we find these rare variants associated with local extremes of gene ...


    pub_type: 杂志文章


    authors: Stuart T,Eichten SR,Cahn J,Karpievitch YV,Borevitz JO,Lister R

    更新日期:2016-12-02 00:00:00

  • Drosophila TRIM32 cooperates with glycolytic enzymes to promote cell growth.

    abstract::Cell growth and/or proliferation may require the reprogramming of metabolic pathways, whereby a switch from oxidative to glycolytic metabolism diverts glycolytic intermediates towards anabolic pathways. Herein, we identify a novel role for TRIM32 in the maintenance of glycolytic flux mediated by biochemical interactio...


    pub_type: 杂志文章


    authors: Bawa S,Brooks DS,Neville KE,Tipping M,Sagar MA,Kollhoff JA,Chawla G,Geisbrecht BV,Tennessen JM,Eliceiri KW,Geisbrecht ER

    更新日期:2020-03-30 00:00:00

  • Distinct stages of the translation elongation cycle revealed by sequencing ribosome-protected mRNA fragments.

    abstract::During translation elongation, the ribosome ratchets along its mRNA template, incorporating each new amino acid and translocating from one codon to the next. The elongation cycle requires dramatic structural rearrangements of the ribosome. We show here that deep sequencing of ribosome-protected mRNA fragments reveals ...


    pub_type: 杂志文章


    authors: Lareau LF,Hite DH,Hogan GJ,Brown PO

    更新日期:2014-05-09 00:00:00

  • BRAF activates PAX3 to control muscle precursor cell migration during forelimb muscle development.

    abstract::Migration of skeletal muscle precursor cells is a key step during limb muscle development and depends on the activity of PAX3 and MET. Here, we demonstrate that BRAF serves a crucial function in formation of limb skeletal muscles during mouse embryogenesis downstream of MET and acts as a potent inducer of myoblast cel...


    pub_type: 杂志文章


    authors: Shin J,Watanabe S,Hoelper S,Krüger M,Kostin S,Pöling J,Kubin T,Braun T

    更新日期:2016-12-01 00:00:00

  • A conserved function for pericentromeric satellite DNA.

    abstract::A universal and unquestioned characteristic of eukaryotic cells is that the genome is divided into multiple chromosomes and encapsulated in a single nucleus. However, the underlying mechanism to ensure such a configuration is unknown. Here, we provide evidence that pericentromeric satellite DNA, which is often regarde...


    pub_type: 杂志文章


    authors: Jagannathan M,Cummings R,Yamashita YM

    更新日期:2018-03-26 00:00:00

  • Venous endothelin modulates responsiveness of cardiac sympathetic axons to arterial semaphorin.

    abstract::Developing neurons of the peripheral nervous system reach their targets via cues that support directional growth, a process known as axon guidance. In investigating how sympathetic axons reach the heart in mice, we discovered that a combination of guidance cues are employed in sequence to refine axon outgrowth, a proc...


    pub_type: 杂志文章


    authors: Poltavski DM,Colombier P,Hu J,Duron A,Black BL,Makita T

    更新日期:2019-02-08 00:00:00

  • The secrets of success.

    abstract::Imaging sperm as they travel through the female reproductive tract has revealed new details about fertilization at the molecular level. ...


    pub_type: 评论,杂志文章


    authors: Komondor KM,Carlson AE

    更新日期:2020-12-02 00:00:00