Attenuation of AMPK signaling by ROQUIN promotes T follicular helper cell formation.


:T follicular helper cells (Tfh) are critical for the longevity and quality of antibody-mediated protection against infection. Yet few signaling pathways have been identified to be unique solely to Tfh development. ROQUIN is a post-transcriptional repressor of T cells, acting through its ROQ domain to destabilize mRNA targets important for Th1, Th17, and Tfh biology. Here, we report that ROQUIN has a paradoxical function on Tfh differentiation mediated by its RING domain: mice with a T cell-specific deletion of the ROQUIN RING domain have unchanged Th1, Th2, Th17, and Tregs during a T-dependent response but show a profoundly defective antigen-specific Tfh compartment. ROQUIN RING signaling directly antagonized the catalytic α1 subunit of adenosine monophosphate-activated protein kinase (AMPK), a central stress-responsive regulator of cellular metabolism and mTOR signaling, which is known to facilitate T-dependent humoral immunity. We therefore unexpectedly uncover a ROQUIN-AMPK metabolic signaling nexus essential for selectively promoting Tfh responses.






Ramiscal RR,Parish IA,Lee-Young RS,Babon JJ,Blagih J,Pratama A,Martin J,Hawley N,Cappello JY,Nieto PF,Ellyard JI,Kershaw NJ,Sweet RA,Goodnow CC,Jones RG,Febbraio MA,Vinuesa CG,Athanasopoulos V




Has Abstract


2015-10-23 00:00:00








  • Crucial role for T cell-intrinsic IL-18R-MyD88 signaling in cognate immune response to intracellular parasite infection.

    abstract::MyD88 is the main adaptor molecule for TLR and IL-1R family members. Here, we demonstrated that T-cell intrinsic MyD88 signaling is required for proliferation, protection from apoptosis and expression of activation/memory genes during infection with the intracellular parasite Trypanosoma cruzi, as evidenced by transcr...


    pub_type: 杂志文章


    authors: Oliveira AC,Gomes-Neto JF,Barbosa CD,Granato A,Reis BS,Santos BM,Fucs R,Canto FB,Nakaya HI,Nóbrega A,Bellio M

    更新日期:2017-09-12 00:00:00

  • Empirical examination of the replicability of associations between brain structure and psychological variables.

    abstract::Linking interindividual differences in psychological phenotype to variations in brain structure is an old dream for psychology and a crucial question for cognitive neurosciences. Yet, replicability of the previously-reported 'structural brain behavior' (SBB)-associations has been questioned, recently. Here, we conduct...


    pub_type: 杂志文章


    authors: Kharabian Masouleh S,Eickhoff SB,Hoffstaedter F,Genon S,Alzheimer's Disease Neuroimaging Initiative.

    更新日期:2019-03-13 00:00:00

  • Multisite dependency of an E3 ligase controls monoubiquitylation-dependent cell fate decisions.

    abstract::Metazoan development depends on tightly regulated gene expression programs that instruct progenitor cells to adopt specialized fates. Recent work found that posttranslational modifications, such as monoubiquitylation, can determine cell fate also independently of effects on transcription, yet how monoubiquitylation is...


    pub_type: 杂志文章


    authors: Werner A,Baur R,Teerikorpi N,Kaya DU,Rape M

    更新日期:2018-07-12 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

  • Sensitivity and kinetics of signal transmission at the first visual synapse differentially impact visually-guided behavior.

    abstract::In the retina, synaptic transmission between photoreceptors and downstream ON-bipolar neurons (ON-BCs) is mediated by a GPCR pathway, which plays an essential role in vision. However, the mechanisms that control signal transmission at this synapse and its relevance to behavior remain poorly understood. In this study w...


    pub_type: 杂志文章


    authors: Sarria I,Pahlberg J,Cao Y,Kolesnikov AV,Kefalov VJ,Sampath AP,Martemyanov KA

    更新日期:2015-04-16 00:00:00

  • Mechanical inhibition of isolated Vo from V/A-ATPase for proton conductance.

    abstract::V-ATPase is an energy converting enzyme, coupling ATP hydrolysis/synthesis in the hydrophilic V1 domain, with proton flow through the Vo membrane domain, via rotation of the central rotor complex relative to the surrounding stator apparatus. Upon dissociation from the V1 domain, the Vo domain of the eukaryotic V-ATPas...


    pub_type: 杂志文章


    authors: Kishikawa JI,Nakanishi A,Furuta A,Kato T,Namba K,Tamakoshi M,Mitsuoka K,Yokoyama K

    更新日期:2020-07-08 00:00:00

  • Mechanism of cargo-directed Atg8 conjugation during selective autophagy.

    abstract::Selective autophagy is mediated by cargo receptors that link the cargo to the isolation membrane via interactions with Atg8 proteins. Atg8 proteins are localized to the membrane in an ubiquitin-like conjugation reaction, but how this conjugation is coupled to the presence of the cargo is unclear. Here we show that the...


    pub_type: 杂志文章


    authors: Fracchiolla D,Sawa-Makarska J,Zens B,Ruiter A,Zaffagnini G,Brezovich A,Romanov J,Runggatscher K,Kraft C,Zagrovic B,Martens S

    更新日期:2016-11-23 00:00:00

  • Impaired skeletal muscle mitochondrial pyruvate uptake rewires glucose metabolism to drive whole-body leanness.

    abstract::Metabolic cycles are a fundamental element of cellular and organismal function. Among the most critical in higher organisms is the Cori Cycle, the systemic cycling between lactate and glucose. Here, skeletal muscle-specific Mitochondrial Pyruvate Carrier (MPC) deletion in mice diverted pyruvate into circulating lactat...


    pub_type: 杂志文章


    authors: Sharma A,Oonthonpan L,Sheldon RD,Rauckhorst AJ,Zhu Z,Tompkins SC,Cho K,Grzesik WJ,Gray LR,Scerbo DA,Pewa AD,Cushing EM,Dyle MC,Cox JE,Adams C,Davies BS,Shields RK,Norris AW,Patti G,Zingman LV,Taylor EB

    更新日期:2019-07-18 00:00:00

  • Correction: BRET-based RAS biosensors that show a novel small molecule is an inhibitor of RAS-effector protein-protein interactions.

    abstract:: ...


    pub_type: 杂志文章,已发布勘误


    authors: Bery N,Cruz-Migoni A,Bataille CJ,Quevedo CE,Tulmin H,Miller A,Russell A,Phillips SE,Carr SB,Rabbitts TH

    更新日期:2018-08-02 00:00:00

  • Blue light-induced LOV domain dimerization enhances the affinity of Aureochrome 1a for its target DNA sequence.

    abstract::The design of synthetic optogenetic tools that allow precise spatiotemporal control of biological processes previously inaccessible to optogenetic control has developed rapidly over the last years. Rational design of such tools requires detailed knowledge of allosteric light signaling in natural photoreceptors. To und...


    pub_type: 杂志文章


    authors: Heintz U,Schlichting I

    更新日期:2016-01-12 00:00:00

  • An extended retinotopic map of mouse cortex.

    abstract::Visual perception and behavior are mediated by cortical areas that have been distinguished using architectonic and retinotopic criteria. We employed fluorescence imaging and GCaMP6 reporter mice to generate retinotopic maps, revealing additional regions of retinotopic organization that extend into barrel and retrosple...


    pub_type: 杂志文章


    authors: Zhuang J,Ng L,Williams D,Valley M,Li Y,Garrett M,Waters J

    更新日期:2017-01-06 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

  • 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

  • Genome rearrangements and pervasive meiotic drive cause hybrid infertility in fission yeast.

    abstract::Hybrid sterility is one of the earliest postzygotic isolating mechanisms to evolve between two recently diverged species. Here we identify causes underlying hybrid infertility of two recently diverged fission yeast species Schizosaccharomyces pombe and S. kambucha, which mate to form viable hybrid diploids that effici...


    pub_type: 杂志文章


    authors: Zanders SE,Eickbush MT,Yu JS,Kang JW,Fowler KR,Smith GR,Malik HS

    更新日期:2014-06-24 00:00:00

  • Adjusting for age improves identification of gut microbiome alterations in multiple diseases.

    abstract::Interaction between disease-microbiome associations and ageing has not been explored in detail. Here, using age/region-matched sub-sets, we analysed the gut microbiome differences across five major diseases in a multi-cohort dataset constituting more than 2500 individuals from 20 to 89 years old. We show that disease-...


    pub_type: 杂志文章


    authors: Ghosh TS,Das M,Jeffery IB,O'Toole PW

    更新日期:2020-03-11 00:00:00

  • Lineage commitment of embryonic cells involves MEK1-dependent clearance of pluripotency regulator Ventx2.

    abstract::During early embryogenesis, cells must exit pluripotency and commit to multiple lineages in all germ-layers. How this transition is operated in vivo is poorly understood. Here, we report that MEK1 and the Nanog-related transcription factor Ventx2 coordinate this transition. MEK1 was required to make Xenopus pluripoten...


    pub_type: 杂志文章


    authors: Scerbo P,Marchal L,Kodjabachian L

    更新日期:2017-06-27 00:00:00

  • Action history influences subsequent movement via two distinct processes.

    abstract::The characteristics of goal-directed actions tend to resemble those of previously executed actions, but it is unclear whether such effects depend strictly on action history, or also reflect context-dependent processes related to predictive motor planning. Here we manipulated the time available to initiate movements af...


    pub_type: 杂志文章


    authors: Marinovic W,Poh E,de Rugy A,Carroll TJ

    更新日期:2017-10-23 00:00:00

  • Decoding gripping force based on local field potentials recorded from subthalamic nucleus in humans.

    abstract::The basal ganglia are known to be involved in the planning, execution and control of gripping force and movement vigour. Here we aim to define the nature of the basal ganglia control signal for force and to decode gripping force based on local field potential (LFP) activities recorded from the subthalamic nucleus (STN...


    pub_type: 杂志文章


    authors: Tan H,Pogosyan A,Ashkan K,Green AL,Aziz T,Foltynie T,Limousin P,Zrinzo L,Hariz M,Brown P

    更新日期:2016-11-18 00:00:00

  • Actin filaments target the oligomeric maturation of the dynamin GTPase Drp1 to mitochondrial fission sites.

    abstract::While the dynamin GTPase Drp1 plays a critical role during mitochondrial fission, mechanisms controlling its recruitment to fission sites are unclear. A current assumption is that cytosolic Drp1 is recruited directly to fission sites immediately prior to fission. Using live-cell microscopy, we find evidence for a diff...


    pub_type: 杂志文章


    authors: Ji WK,Hatch AL,Merrill RA,Strack S,Higgs HN

    更新日期:2015-11-26 00:00:00

  • Different CFTR modulator combinations downregulate inflammation differently in cystic fibrosis.

    abstract::Previously, we showed that serum and monocytes from patients with CF exhibit an enhanced NLRP3-inflammasome signature with increased IL-18, IL-1β, caspase-1 activity and ASC speck release (Scambler et al. eLife 2019). Here we show that CFTR modulators down regulate this exaggerated proinflammatory response following L...


    pub_type: 杂志文章


    authors: Jarosz-Griffiths HH,Scambler T,Wong CH,Lara-Reyna S,Holbrook J,Martinon F,Savic S,Whitaker P,Etherington C,Spoletini G,Clifton I,Mehta A,McDermott MF,Peckham D

    更新日期:2020-03-02 00:00:00

  • Mycobacterium tuberculosis induces decelerated bioenergetic metabolism in human macrophages.

    abstract::How Mycobacterium tuberculosis (Mtb) rewires macrophage energy metabolism to facilitate survival is poorly characterized. Here, we used extracellular flux analysis to simultaneously measure the rates of glycolysis and respiration in real time. Mtb infection induced a quiescent energy phenotype in human monocyte-derive...


    pub_type: 杂志文章


    authors: Cumming BM,Addicott KW,Adamson JH,Steyn AJ

    更新日期:2018-11-16 00:00:00

  • Paying the costs of reproduction.

    abstract::When a female fly mates it produces a hormone that increases the size of its midgut and enhances fat metabolism in order to provide the energy needed for reproduction. ...


    pub_type: 评论,杂志文章


    authors: Flatt T

    更新日期:2015-07-28 00:00:00

  • Cortex-dependent recovery of unassisted hindlimb locomotion after complete spinal cord injury in adult rats.

    abstract::After paralyzing spinal cord injury the adult nervous system has little ability to 'heal' spinal connections, and it is assumed to be unable to develop extra-spinal recovery strategies to bypass the lesion. We challenge this assumption, showing that completely spinalized adult rats can recover unassisted hindlimb weig...


    pub_type: 杂志文章


    authors: Manohar A,Foffani G,Ganzer PD,Bethea JR,Moxon KA

    更新日期:2017-06-29 00:00:00

  • NMDA spikes mediate amplification of inputs in the rat piriform cortex.

    abstract::The piriform cortex (PCx) receives direct input from the olfactory bulb (OB) and is the brain's main station for odor recognition and memory. The transformation of the odor code from OB to PCx is profound: mitral and tufted cells in olfactory glomeruli respond to individual odorant molecules, whereas pyramidal neurons...


    pub_type: 杂志文章


    authors: Kumar A,Schiff O,Barkai E,Mel BW,Poleg-Polsky A,Schiller J

    更新日期:2018-12-21 00:00:00

  • Phylogenomic analysis supports the ancestral presence of LPS-outer membranes in the Firmicutes.

    abstract::One of the major unanswered questions in evolutionary biology is when and how the transition between diderm (two membranes) and monoderm (one membrane) cell envelopes occurred in Bacteria. The Negativicutes and the Halanaerobiales belong to the classically monoderm Firmicutes, but possess outer membranes with lipopoly...


    pub_type: 杂志文章


    authors: Antunes LC,Poppleton D,Klingl A,Criscuolo A,Dupuy B,Brochier-Armanet C,Beloin C,Gribaldo S

    更新日期:2016-08-31 00:00:00

  • Metabolic control of cellular immune-competency by odors in Drosophila.

    abstract::Studies in different animal model systems have revealed the impact of odors on immune cells; however, any understanding on why and how odors control cellular immunity remained unclear. We find that Drosophila employ an olfactory-immune cross-talk to tune a specific cell type, the lamellocytes, from hematopoietic-proge...


    pub_type: 杂志文章


    authors: Madhwal S,Shin M,Kapoor A,Goyal M,Joshi MK,Ur Rehman PM,Gor K,Shim J,Mukherjee T

    更新日期:2020-12-29 00:00:00

  • Deep generative models for T cell receptor protein sequences.

    abstract::Probabilistic models of adaptive immune repertoire sequence distributions can be used to infer the expansion of immune cells in response to stimulus, differentiate genetic from environmental factors that determine repertoire sharing, and evaluate the suitability of various target immune sequences for stimulation via v...


    pub_type: 杂志文章


    authors: Davidsen K,Olson BJ,DeWitt WS 3rd,Feng J,Harkins E,Bradley P,Matsen FA 4th

    更新日期:2019-09-05 00:00:00

  • Phenotypic diversity and temporal variability in a bacterial signaling network revealed by single-cell FRET.

    abstract::We present in vivo single-cell FRET measurements in the Escherichia coli chemotaxis system that reveal pervasive signaling variability, both across cells in isogenic populations and within individual cells over time. We quantify cell-to-cell variability of adaptation, ligand response, as well as steady-state output le...


    pub_type: 杂志文章


    authors: Keegstra JM,Kamino K,Anquez F,Lazova MD,Emonet T,Shimizu TS

    更新日期:2017-12-12 00:00:00

  • Cryo-EM structure of a late pre-40S ribosomal subunit from Saccharomyces cerevisiae.

    abstract::Mechanistic understanding of eukaryotic ribosome formation requires a detailed structural knowledge of the numerous assembly intermediates, generated along a complex pathway. Here, we present the structure of a late pre-40S particle at 3.6 Å resolution, revealing in molecular detail how assembly factors regulate the t...


    pub_type: 杂志文章


    authors: Heuer A,Thomson E,Schmidt C,Berninghausen O,Becker T,Hurt E,Beckmann R

    更新日期:2017-11-20 00:00:00

  • Quantitative differences, qualitative outcomes.

    abstract::Fruit fly neuroblasts can either self-renew, rest or take on a specialized form, depending on the levels of a protein called Prospero. ...


    pub_type: 杂志文章


    authors: Pollarolo G,Gonzalez C

    更新日期:2014-10-29 00:00:00