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








  • The transcription factor Pitx2 positions the embryonic axis and regulates twinning.

    abstract::Embryonic polarity of invertebrates, amphibians and fish is specified largely by maternal determinants, which fixes cell fates early in development. In contrast, amniote embryos remain plastic and can form multiple individuals until gastrulation. How is their polarity determined? In the chick embryo, the earliest know...


    pub_type: 杂志文章


    authors: Torlopp A,Khan MA,Oliveira NM,Lekk I,Soto-Jiménez LM,Sosinsky A,Stern CD

    更新日期:2014-12-11 00:00:00

  • How geometry shapes division of labor.

    abstract::A mathematical model shows how the shape of early multicellular organisms may have helped cells evolve specialized roles. ...


    pub_type: 评论,杂志文章


    authors: Staps M,Tarnita C

    更新日期:2020-11-03 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

  • 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

  • The impact of measles immunization campaigns in India using a nationally representative sample of 27,000 child deaths.

    abstract::India comprises much of the persisting global childhood measles mortality. India implemented a mass second-dose measles immunization campaign in 2010. We used interrupted time series and multilevel regression to quantify the campaign's impact on measles mortality using the nationally representative Million Death Study...


    pub_type: 杂志文章


    authors: Wong BK,Fadel SA,Awasthi S,Khera A,Kumar R,Menon G,Jha P

    更新日期:2019-03-05 00:00:00

  • Lipid polarity gradient formed by ω-hydroxy lipids in tear film prevents dry eye disease.

    abstract::Meibum lipids form a lipid layer on the outermost side of the tear film and function to prevent water evaporation and reduce surface tension. (O-Acyl)-ω-hydroxy fatty acids (OAHFAs), a subclass of these lipids, are thought to be involved in connecting the lipid and aqueous layers in tears, although their actual functi...


    pub_type: 杂志文章


    authors: Miyamoto M,Sassa T,Sawai M,Kihara A

    更新日期:2020-04-07 00:00:00

  • Srsf10 and the minor spliceosome control tissue-specific and dynamic SR protein expression.

    abstract::Minor and major spliceosomes control splicing of distinct intron types and are thought to act largely independent of one another. SR proteins are essential splicing regulators mostly connected to the major spliceosome. Here, we show that Srsf10 expression is controlled through an autoregulated minor intron, tightly co...


    pub_type: 杂志文章


    authors: Meinke S,Goldammer G,Weber AI,Tarabykin V,Neumann A,Preussner M,Heyd F

    更新日期:2020-04-27 00:00:00

  • All Purkinje cells are not created equal.

    abstract::Although the wiring of the cerebellar cortex appears to be uniform, the neurons in this region of the brain behave more differently from each other than previously thought. ...


    pub_type: 评论,杂志文章


    authors: Albergaria C,Carey MR

    更新日期:2014-06-10 00:00:00

  • Telomeric double-strand DNA-binding proteins DTN-1 and DTN-2 ensure germline immortality in Caenorhabditis elegans.

    abstract::Telomeres are nucleoprotein complexes at the ends of chromosomes and are indispensable for the protection and lengthening of terminal DNA. Despite the evolutionarily conserved roles of telomeres, the telomeric double-strand DNA (dsDNA)-binding proteins have evolved rapidly. Here, we identified double-strand telomeric ...


    pub_type: 杂志文章


    authors: Yamamoto I,Zhang K,Zhang J,Vorontsov E,Shibuya H

    更新日期:2021-01-21 00:00:00

  • Ribosome biogenesis restricts innate immune responses to virus infection and DNA.

    abstract::Ribosomes are universally important in biology and their production is dysregulated by developmental disorders, cancer, and virus infection. Although presumed required for protein synthesis, how ribosome biogenesis impacts virus reproduction and cell-intrinsic immune responses remains untested. Surprisingly, we find t...


    pub_type: 杂志文章


    authors: Bianco C,Mohr I

    更新日期:2019-12-16 00:00:00

  • Alzheimer's disease risk gene BIN1 induces Tau-dependent network hyperexcitability.

    abstract::Genome-wide association studies identified the BIN1 locus as a leading modulator of genetic risk in Alzheimer's disease (AD). One limitation in understanding BIN1's contribution to AD is its unknown function in the brain. AD-associated BIN1 variants are generally noncoding and likely change expression. Here, we determ...


    pub_type: 杂志文章


    authors: Voskobiynyk Y,Roth JR,Cochran JN,Rush T,Carullo NV,Mesina JS,Waqas M,Vollmer RM,Day JJ,McMahon LL,Roberson ED

    更新日期:2020-07-13 00:00:00

  • Metabolic profiling during malaria reveals the role of the aryl hydrocarbon receptor in regulating kidney injury.

    abstract::Systemic metabolic reprogramming induced by infection exerts profound, pathogen-specific effects on infection outcome. Here, we detail the host immune and metabolic response during sickness and recovery in a mouse model of malaria. We describe extensive alterations in metabolism during acute infection, and identify in...


    pub_type: 杂志文章


    authors: Lissner MM,Cumnock K,Davis NM,Vilches-Moure JG,Basak P,Navarrete DJ,Allen JA,Schneider D

    更新日期:2020-10-06 00:00:00

  • All about the RNA after all.

    abstract::RNA molecules cause the proteins involved in the formation of germ granules to coalesce into liquid droplets. ...


    pub_type: 评论,杂志文章


    authors: Trcek T,Lehmann R

    更新日期:2017-01-24 00:00:00

  • Regulation of signaling directionality revealed by 3D snapshots of a kinase:regulator complex in action.

    abstract::Two-component systems (TCS) are protein machineries that enable cells to respond to input signals. Histidine kinases (HK) are the sensory component, transferring information toward downstream response regulators (RR). HKs transfer phosphoryl groups to their specific RRs, but also dephosphorylate them, overall ensuring...


    pub_type: 杂志文章


    authors: Trajtenberg F,Imelio JA,Machado MR,Larrieux N,Marti MA,Obal G,Mechaly AE,Buschiazzo A

    更新日期:2016-12-12 00:00:00

  • High throughput in vivo functional validation of candidate congenital heart disease genes in Drosophila.

    abstract::Genomic sequencing has implicated large numbers of genes and de novo mutations as potential disease risk factors. A high throughput in vivo model system is needed to validate gene associations with pathology. We developed a Drosophila-based functional system to screen candidate disease genes identified from Congenital...


    pub_type: 杂志文章


    authors: Zhu JY,Fu Y,Nettleton M,Richman A,Han Z

    更新日期:2017-01-20 00:00:00

  • What does cannabis do to the brain before birth?

    abstract::Being exposed to cannabinoids in the womb has different consequences for male and female rats. ...


    pub_type: 评论,杂志文章


    authors: Musardo S,Bellone C

    更新日期:2018-09-28 00:00:00

  • Neural tuning matches frequency-dependent time differences between the ears.

    abstract::The time it takes a sound to travel from source to ear differs between the ears and creates an interaural delay. It varies systematically with spatial direction and is generally modeled as a pure time delay, independent of frequency. In acoustical recordings, we found that interaural delay varies with frequency at a f...


    pub_type: 杂志文章


    authors: Benichoux V,Fontaine B,Franken TP,Karino S,Joris PX,Brette R

    更新日期:2015-04-27 00:00:00

  • Selectivity to approaching motion in retinal inputs to the dorsal visual pathway.

    abstract::To efficiently navigate through the environment and avoid potential threats, an animal must quickly detect the motion of approaching objects. Current models of primate vision place the origins of this complex computation in the visual cortex. Here, we report that detection of approaching motion begins in the retina. S...


    pub_type: 杂志文章


    authors: Appleby TR,Manookin MB

    更新日期:2020-02-24 00:00:00

  • Target-specific membrane potential dynamics of neocortical projection neurons during goal-directed behavior.

    abstract::Goal-directed behavior involves distributed neuronal circuits in the mammalian brain, including diverse regions of neocortex. However, the cellular basis of long-range cortico-cortical signaling during goal-directed behavior is poorly understood. Here, we recorded membrane potential of excitatory layer 2/3 pyramidal n...


    pub_type: 杂志文章


    authors: Yamashita T,Petersen CCh

    更新日期:2016-06-21 00:00:00

  • PROP1 triggers epithelial-mesenchymal transition-like process in pituitary stem cells.

    abstract::Mutations in PROP1 are the most common cause of hypopituitarism in humans; therefore, unraveling its mechanism of action is highly relevant from a therapeutic perspective. Our current understanding of the role of PROP1 in the pituitary gland is limited to the repression and activation of the pituitary transcription fa...


    pub_type: 杂志文章


    authors: Pérez Millán MI,Brinkmeier ML,Mortensen AH,Camper SA

    更新日期:2016-06-28 00:00:00

  • Extraordinary effects of unnatural pairings.

    abstract::Engineered molecules based on human cytokines have potential uses in research and medicine. ...


    pub_type: 评论,杂志文章


    authors: Villarino A,O'Shea JJ

    更新日期:2017-05-12 00:00:00

  • Layer 2/3 pyramidal cells in the medial prefrontal cortex moderate stress induced depressive behaviors.

    abstract::Major depressive disorder (MDD) is a prevalent illness that can be precipitated by acute or chronic stress. Studies of patients with Wolfram syndrome and carriers have identified Wfs1 mutations as causative for MDD. The medial prefrontal cortex (mPFC) is known to be involved in depression and behavioral resilience, al...


    pub_type: 杂志文章


    authors: Shrestha P,Mousa A,Heintz N

    更新日期:2015-09-15 00:00:00

  • Perinatal hormones favor CC17 group B Streptococcus intestinal translocation through M cells and hypervirulence in neonates.

    abstract::Group B Streptococcus (GBS) is the leading cause of invasive bacterial neonatal infections. Late-onset diseases (LOD) occur between 7 and 89 days of life and are largely due to the CC17 GBS hypervirulent clone. We studied the impact of estradiol (E2) and progesterone (P4), which impregnate the fetus during pregnancy, ...


    pub_type: 杂志文章


    authors: Hays C,Touak G,Bouaboud A,Fouet A,Guignot J,Poyart C,Tazi A

    更新日期:2019-11-11 00:00:00

  • Protein aggregates are associated with replicative aging without compromising protein quality control.

    abstract::Differentiation of cellular lineages is facilitated by asymmetric segregation of fate determinants between dividing cells. In budding yeast, various aging factors segregate to the aging (mother)-lineage, with poorly understood consequences. In this study, we show that yeast mother cells form a protein aggregate during...


    pub_type: 杂志文章


    authors: Saarikangas J,Barral Y

    更新日期:2015-11-06 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

  • GnT1IP-L specifically inhibits MGAT1 in the Golgi via its luminal domain.

    abstract::Mouse GnT1IP-L, and membrane-bound GnT1IP-S (MGAT4D) expressed in cultured cells inhibit MGAT1, the N-acetylglucosaminyltransferase that initiates the synthesis of hybrid and complex N-glycans. However, it is not known where in the secretory pathway GnT1IP-L inhibits MGAT1, nor whether GnT1IP-L inhibits other N-glycan...


    pub_type: 杂志文章


    authors: Huang HH,Hassinen A,Sundaram S,Spiess AN,Kellokumpu S,Stanley P

    更新日期:2015-09-15 00:00:00

  • Atomic mutagenesis in ion channels with engineered stoichiometry.

    abstract::C-type inactivation of potassium channels fine-tunes the electrical signaling in excitable cells through an internal timing mechanism that is mediated by a hydrogen bond network in the channels' selectively filter. Previously, we used nonsense suppression to highlight the role of the conserved Trp434-Asp447 indole hyd...


    pub_type: 杂志文章


    authors: Lueck JD,Mackey AL,Infield DT,Galpin JD,Li J,Roux B,Ahern CA

    更新日期:2016-10-06 00:00:00

  • Molecular insights into the origin of the Hox-TALE patterning system.

    abstract::Despite tremendous body form diversity in nature, bilaterian animals share common sets of developmental genes that display conserved expression patterns in the embryo. Among them are the Hox genes, which define different identities along the anterior-posterior axis. Hox proteins exert their function by interaction wit...


    pub_type: 杂志文章


    authors: Hudry B,Thomas-Chollier M,Volovik Y,Duffraisse M,Dard A,Frank D,Technau U,Merabet S

    更新日期:2014-03-18 00:00:00

  • Functional role of the type 1 pilus rod structure in mediating host-pathogen interactions.

    abstract::Uropathogenic E. coli (UPEC), which cause urinary tract infections (UTI), utilize type 1 pili, a chaperone usher pathway (CUP) pilus, to cause UTI and colonize the gut. The pilus rod, comprised of repeating FimA subunits, provides a structural scaffold for displaying the tip adhesin, FimH. We solved the 4.2 Å resoluti...


    pub_type: 杂志文章


    authors: Spaulding CN,Schreiber HL 4th,Zheng W,Dodson KW,Hazen JE,Conover MS,Wang F,Svenmarker P,Luna-Rico A,Francetic O,Andersson M,Hultgren S,Egelman EH

    更新日期:2018-01-18 00:00:00

  • Registered report: Coding-independent regulation of the tumor suppressor PTEN by competing endogenous mRNAs.

    abstract::The Reproducibility Project: Cancer Biology seeks to address growing concerns about reproducibility in scientific research by conducting replications of selected experiments from a number of high-profile papers in the field of cancer biology. The papers, which were published between 2010 and 2012, were selected on the...


    pub_type: 杂志文章


    authors: Phelps M,Coss C,Wang H,Cook M,Reproducibility Project: Cancer Biology.,Reproducibility Project Cancer Biology.

    更新日期:2016-03-01 00:00:00