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








  • Role of SAGA in the asymmetric segregation of DNA circles during yeast ageing.

    abstract::In eukaryotes, intra-chromosomal recombination generates DNA circles, but little is known about how cells react to them. In yeast, partitioning of such circles to the mother cell at mitosis ensures their loss from the population but promotes replicative ageing. Nevertheless, the mechanisms of partitioning are debated....


    pub_type: 杂志文章


    authors: Denoth-Lippuner A,Krzyzanowski MK,Stober C,Barral Y

    更新日期:2014-11-17 00:00:00

  • Embryonic hematopoiesis modulates the inflammatory response and larval hematopoiesis in Drosophila.

    abstract::Recent lineage tracing analyses have significantly improved our understanding of immune system development and highlighted the importance of the different hematopoietic waves. The current challenge is to understand whether these waves interact and whether this affects the function of the immune system. Here we report ...


    pub_type: 杂志文章


    authors: Bazzi W,Cattenoz PB,Delaporte C,Dasari V,Sakr R,Yuasa Y,Giangrande A

    更新日期:2018-07-11 00:00:00

  • Dissection of specific binding of HIV-1 Gag to the 'packaging signal' in viral RNA.

    abstract::Selective packaging of HIV-1 genomic RNA (gRNA) requires the presence of a cis-acting RNA element called the 'packaging signal' (Ψ). However, the mechanism by which Ψ promotes selective packaging of the gRNA is not well understood. We used fluorescence correlation spectroscopy and quenching data to monitor the binding...


    pub_type: 杂志文章


    authors: Comas-Garcia M,Datta SA,Baker L,Varma R,Gudla PR,Rein A

    更新日期:2017-07-20 00:00:00

  • Learning is enhanced by tailoring instruction to individual genetic differences.

    abstract::It is widely argued that personalized instruction based on individual differences in learning styles or genetic predispositions could improve learning outcomes. However, this proposition has resisted clear demonstration in human studies, where it is difficult to control experience and quantify outcomes. Here, we take ...


    pub_type: 杂志文章


    authors: Mets DG,Brainard MS

    更新日期:2019-09-17 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

  • Is it possible to reconstruct an accurate cell lineage using CRISPR recorders?

    abstract::Cell lineages provide the framework for understanding how cell fates are decided during development. Describing cell lineages in most organisms is challenging; even a fruit fly larva has ~50,000 cells and a small mammal has >1 billion cells. Recently, the idea of applying CRISPR to induce mutations during development,...


    pub_type: 杂志文章


    authors: Salvador-Martínez I,Grillo M,Averof M,Telford MJ

    更新日期:2019-01-28 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

  • Semaphorin 5A inhibits synaptogenesis in early postnatal- and adult-born hippocampal dentate granule cells.

    abstract::Human SEMAPHORIN 5A (SEMA5A) is an autism susceptibility gene; however, its function in brain development is unknown. In this study, we show that mouse Sema5A negatively regulates synaptogenesis in early, developmentally born, hippocampal dentate granule cells (GCs). Sema5A is strongly expressed by GCs and regulates d...


    pub_type: 杂志文章


    authors: Duan Y,Wang SH,Song J,Mironova Y,Ming GL,Kolodkin AL,Giger RJ

    更新日期:2014-10-14 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

  • The major β-catenin/E-cadherin junctional binding site is a primary molecular mechano-transductor of differentiation in vivo.

    abstract::In vivo, the primary molecular mechanotransductive events mechanically initiating cell differentiation remain unknown. Here we find the molecular stretching of the highly conserved Y654-β-catenin-D665-E-cadherin binding site as mechanically induced by tissue strain. It triggers the increase of accessibility of the Y65...


    pub_type: 杂志文章


    authors: Röper JC,Mitrossilis D,Stirnemann G,Waharte F,Brito I,Fernandez-Sanchez ME,Baaden M,Salamero J,Farge E

    更新日期:2018-07-19 00:00:00

  • Tgfβ signaling is critical for maintenance of the tendon cell fate.

    abstract::Studies of cell fate focus on specification, but little is known about maintenance of the differentiated state. In this study, we find that the mouse tendon cell fate requires continuous maintenance in vivo and identify an essential role for TGFβ signaling in maintenance of the tendon cell fate. To examine the role of...


    pub_type: 杂志文章


    authors: Tan GK,Pryce BA,Stabio A,Brigande JV,Wang C,Xia Z,Tufa SF,Keene DR,Schweitzer R

    更新日期:2020-01-21 00:00:00

  • Attention stabilizes the shared gain of V4 populations.

    abstract::Responses of sensory neurons represent stimulus information, but are also influenced by internal state. For example, when monkeys direct their attention to a visual stimulus, the response gain of specific subsets of neurons in visual cortex changes. Here, we develop a functional model of population activity to investi...


    pub_type: 杂志文章


    authors: Rabinowitz NC,Goris RL,Cohen M,Simoncelli EP

    更新日期:2015-11-02 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

  • ATR expands embryonic stem cell fate potential in response to replication stress.

    abstract::Unrepaired DNA damage during embryonic development can be potentially inherited by a large population of cells. However, the quality control mechanisms that minimize the contribution of damaged cells to developing embryos remain poorly understood. Here, we uncovered an ATR- and CHK1-mediated transcriptional response t...


    pub_type: 杂志文章


    authors: Atashpaz S,Samadi Shams S,Gonzalez JM,Sebestyén E,Arghavanifard N,Gnocchi A,Albers E,Minardi S,Faga G,Soffientini P,Allievi E,Cancila V,Bachi A,Fernández-Capetillo Ó,Tripodo C,Ferrari F,López-Contreras AJ,Costanzo V

    更新日期:2020-03-12 00:00:00

  • Multiplexed genetic engineering of human hematopoietic stem and progenitor cells using CRISPR/Cas9 and AAV6.

    abstract::Precise and efficient manipulation of genes is crucial for understanding the molecular mechanisms that govern human hematopoiesis and for developing novel therapies for diseases of the blood and immune system. Current methods do not enable precise engineering of complex genotypes that can be easily tracked in a mixed ...


    pub_type: 杂志文章


    authors: Bak RO,Dever DP,Reinisch A,Cruz Hernandez D,Majeti R,Porteus MH

    更新日期:2017-09-28 00:00:00

  • Epidermal barrier defects link atopic dermatitis with altered skin cancer susceptibility.

    abstract::Atopic dermatitis can result from loss of structural proteins in the outermost epidermal layers, leading to a defective epidermal barrier. To test whether this influences tumour formation, we chemically induced tumours in EPI-/- mice, which lack three barrier proteins-Envoplakin, Periplakin, and Involucrin. EPI-/- mic...


    pub_type: 杂志文章


    authors: Cipolat S,Hoste E,Natsuga K,Quist SR,Watt FM

    更新日期:2014-05-05 00:00:00

  • Metformin inhibits mitochondrial complex I of cancer cells to reduce tumorigenesis.

    abstract::Recent epidemiological and laboratory-based studies suggest that the anti-diabetic drug metformin prevents cancer progression. How metformin diminishes tumor growth is not fully understood. In this study, we report that in human cancer cells, metformin inhibits mitochondrial complex I (NADH dehydrogenase) activity and...


    pub_type: 杂志文章


    authors: Wheaton WW,Weinberg SE,Hamanaka RB,Soberanes S,Sullivan LB,Anso E,Glasauer A,Dufour E,Mutlu GM,Budigner GS,Chandel NS

    更新日期:2014-05-13 00:00:00

  • A new regulator of caveolae signalling.

    abstract::Cavin-3 regulates metabolism and cell proliferation by coordinating the activities of growth factor signalling cascades. ...


    pub_type: 评论,杂志文章


    authors: Whitmarsh AJ

    更新日期:2013-09-24 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

  • The ribosomal protein Asc1/RACK1 is required for efficient translation of short mRNAs.

    abstract::Translation is a core cellular process carried out by a highly conserved macromolecular machine, the ribosome. There has been remarkable evolutionary adaptation of this machine through the addition of eukaryote-specific ribosomal proteins whose individual effects on ribosome function are largely unknown. Here we show ...


    pub_type: 杂志文章


    authors: Thompson MK,Rojas-Duran MF,Gangaramani P,Gilbert WV

    更新日期:2016-04-27 00:00:00

  • Multivalency of NDC80 in the outer kinetochore is essential to track shortening microtubules and generate forces.

    abstract::Presence of multiple copies of the microtubule-binding NDC80 complex is an evolutionary conserved feature of kinetochores, points of attachment of chromosomes to spindle microtubules. This may enable multivalent attachments to microtubules, with implications that remain unexplored. Using recombinant human kinetochore ...


    pub_type: 杂志文章


    authors: Volkov VA,Huis In 't Veld PJ,Dogterom M,Musacchio A

    更新日期:2018-04-09 00:00:00

  • Entrained neuronal activity to periodic visual stimuli in the primate striatum compared with the cerebellum.

    abstract::Rhythmic events recruit neuronal activity in the basal ganglia and cerebellum, but their roles remain elusive. In monkeys attempting to detect a single omission of isochronous visual stimulus, we found that neurons in the caudate nucleus showed increased activity for each stimulus in sequence, while those in the cereb...


    pub_type: 杂志文章


    authors: Kameda M,Ohmae S,Tanaka M

    更新日期:2019-09-06 00:00:00

  • How prolonged expression of Hunchback, a temporal transcription factor, re-wires locomotor circuits.

    abstract::How circuits assemble starting from stem cells is a fundamental question in developmental neurobiology. We test the hypothesis that, in neuronal stem cells, temporal transcription factors predictably control neuronal terminal features and circuit assembly. Using the Drosophila motor system, we manipulate expression of...


    pub_type: 杂志文章


    authors: Meng JL,Marshall ZD,Lobb-Rabe M,Heckscher ES

    更新日期:2019-09-10 00:00:00

  • The many mysteries of Homo naledi.

    abstract::More than 1500 fossils from the Rising Star cave system in South Africa have been assigned to a new human species, Homo naledi, which displays a unique combination of primitive and derived traits throughout the skeleton. ...


    pub_type: 评论,杂志文章


    authors: Stringer C

    更新日期:2015-09-10 00:00:00

  • Gating of neural error signals during motor learning.

    abstract::Cerebellar climbing fiber activity encodes performance errors during many motor learning tasks, but the role of these error signals in learning has been controversial. We compared two motor learning paradigms that elicited equally robust putative error signals in the same climbing fibers: learned increases and decreas...


    pub_type: 杂志文章


    authors: Kimpo RR,Rinaldi JM,Kim CK,Payne HL,Raymond JL

    更新日期:2014-04-22 00:00:00

  • Large domains of heterochromatin direct the formation of short mitotic chromosome loops.

    abstract::During mitosis chromosomes reorganise into highly compact, rod-shaped forms, thought to consist of consecutive chromatin loops around a central protein scaffold. Condensin complexes are involved in chromatin compaction, but the contribution of other chromatin proteins, DNA sequence and histone modifications is less un...


    pub_type: 杂志文章


    authors: Fitz-James MH,Tong P,Pidoux AL,Ozadam H,Yang L,White SA,Dekker J,Allshire RC

    更新日期:2020-09-11 00:00:00

  • Cell-type-specific control of basolateral amygdala neuronal circuits via entorhinal cortex-driven feedforward inhibition.

    abstract::The basolateral amygdala (BLA) plays a vital role in associating sensory stimuli with salient valence information. Excitatory principal neurons (PNs) undergo plastic changes to encode this association; however, local BLA inhibitory interneurons (INs) gate PN plasticity via feedforward inhibition (FFI). Despite literat...


    pub_type: 杂志文章


    authors: Guthman EM,Garcia JD,Ma M,Chu P,Baca SM,Smith KR,Restrepo D,Huntsman MM

    更新日期:2020-01-09 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

  • 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

  • Coronary arterial development is regulated by a Dll4-Jag1-EphrinB2 signaling cascade.

    abstract::Coronaries are essential for myocardial growth and heart function. Notch is crucial for mouse embryonic angiogenesis, but its role in coronary development remains uncertain. We show Jag1, Dll4 and activated Notch1 receptor expression in sinus venosus (SV) endocardium. Endocardial Jag1 removal blocks SV capillary sprou...


    pub_type: 杂志文章


    authors: Travisano SI,Oliveira VL,Prados B,Grego-Bessa J,Piñeiro-Sabarís R,Bou V,Gómez MJ,Sánchez-Cabo F,MacGrogan D,de la Pompa JL

    更新日期:2019-12-04 00:00:00