Opposing effects of PKCtheta and WASp on symmetry breaking and relocation of the immunological synapse.


:The immunological synapse (IS) is a junction between the T cell and antigen-presenting cell and is composed of supramolecular activation clusters (SMACs). No studies have been published on naive T cell IS dynamics. Here, we find that IS formation during antigen recognition comprises cycles of stable IS formation and autonomous naive T cell migration. The migration phase is driven by PKCtheta, which is localized to the F-actin-dependent peripheral (p)SMAC. PKCtheta(-/-) T cells formed hyperstable IS in vitro and in vivo and, like WT cells, displayed fast oscillations in the distal SMAC, but they showed reduced slow oscillations in pSMAC integrity. IS reformation is driven by the Wiscott Aldrich Syndrome protein (WASp). WASp(-/-) T cells displayed normal IS formation but were unable to reform IS after migration unless PKCtheta was inhibited. Thus, opposing effects of PKCtheta and WASp control IS stability through pSMAC symmetry breaking and reformation.






Sims TN,Soos TJ,Xenias HS,Dubin-Thaler B,Hofman JM,Waite JC,Cameron TO,Thomas VK,Varma R,Wiggins CH,Sheetz MP,Littman DR,Dustin ML




Has Abstract


2007-05-18 00:00:00
















  • Influence of metabolism on epigenetics and disease.

    abstract::Chemical modifications of histones and DNA, such as histone methylation, histone acetylation, and DNA methylation, play critical roles in epigenetic gene regulation. Many of the enzymes that add or remove such chemical modifications are known, or might be suspected, to be sensitive to changes in intracellular metaboli...


    pub_type: 杂志文章,评审


    authors: Kaelin WG Jr,McKnight SL

    更新日期:2013-03-28 00:00:00

  • Stable Chromosome Condensation Revealed by Chromosome Conformation Capture.

    abstract::Chemical cross-linking and DNA sequencing have revealed regions of intra-chromosomal interaction, referred to as topologically associating domains (TADs), interspersed with regions of little or no interaction, in interphase nuclei. We find that TADs and the regions between them correspond with the bands and interbands...


    pub_type: 杂志文章


    authors: Eagen KP,Hartl TA,Kornberg RD

    更新日期:2015-11-05 00:00:00

  • Axonal remodeling and synaptic differentiation in the cerebellum is regulated by WNT-7a signaling.

    abstract::Synapse formation requires changes in cell morphology and the upregulation and localization of synaptic proteins. In the cerebellum, mossy fibers undergo extensive remodeling as they contact several granule cells and form complex, multisynaptic glomerular rosettes. Here we show that granule cells secrete factors that ...


    pub_type: 杂志文章


    authors: Hall AC,Lucas FR,Salinas PC

    更新日期:2000-03-03 00:00:00

  • brlA is necessary and sufficient to direct conidiophore development in Aspergillus nidulans.

    abstract::The brlA gene of A. nidulans mediates the developmental switch from the indeterminate, apical growth pattern of vegetative cells to the budding growth pattern of conidiophores. brlA encodes a 432 amino acid polypeptide containing two directly repeated motifs resembling the Zn(II) coordination sites first recognized in...


    pub_type: 杂志文章


    authors: Adams TH,Boylan MT,Timberlake WE

    更新日期:1988-07-29 00:00:00

  • The controlling element Ds at the Shrunken locus in Zea mays: structure of the unstable sh-m5933 allele and several revertants.

    abstract::We have analyzed the structure of the Shrunken (Sh) locus in a strain containing an unstable recessive mutation, sh-m5933, caused by the transposable controlling element Dissociation (Ds). We have also analyzed nine spontaneous Sh revertant alleles. The sh-m5933 allele contains a 30 kb insertion at the Sh locus, as we...


    pub_type: 杂志文章


    authors: Courage-Tebbe U,Döring HP,Fedoroff N,Starlinger P

    更新日期:1983-09-01 00:00:00

  • Insertion of a multispanning membrane protein occurs sequentially and requires only one signal sequence.

    abstract::To study the insertion of multispanning membrane proteins into the endoplasmic reticulum, we constructed novel proteins on the cDNA level by repeating, up to four times, the internal signal-anchor domain of the asialoglycoprotein receptor H1. Upon in vitro translation in the presence of microsomes, these polypeptides ...


    pub_type: 杂志文章


    authors: Wessels HP,Spiess M

    更新日期:1988-10-07 00:00:00

  • Protein kinase C phosphorylation at Thr 654 of the unoccupied EGF receptor and EGF binding regulate functional receptor loss by independent mechanisms.

    abstract::To test the functional consequence of phosphorylation of the EGF receptor at Thr 654 by protein kinase C, the normal Thr 654 human EGF receptor cDNA or a mutant encoding an Ala 654 were expressed in heterologous cells. In cell lines expressing both the Thr 654 and Ala 654 receptors, functional cell-surface Thr 654 rec...


    pub_type: 杂志文章


    authors: Lin CR,Chen WS,Lazar CS,Carpenter CD,Gill GN,Evans RM,Rosenfeld MG

    更新日期:1986-03-28 00:00:00

  • Protein phosphorylation at tyrosine is induced by the v-erbB gene product in vivo and in vitro.

    abstract::The v-erbB gene product of avian erythroblastosis virus (AEV) has extensive homology with the receptor for epidermal growth factor (EGF). We report here that chicken embryo fibroblasts (CEF) transformed by AEV show enhanced tyrosine phosphorylation of a number of cellular polypeptides, including the 36 kd protein, whi...


    pub_type: 杂志文章


    authors: Gilmore T,DeClue JE,Martin GS

    更新日期:1985-03-01 00:00:00

  • Splicing misplaced.

    abstract::Newly synthesized transcripts are usually spliced during transcription or immediately thereafter. So pre-mRNA splicing has been presumed to occur exclusively in the cell nucleus. In this issue of Cell, Denis et al. (2005) now report the presence of functional spliceosomes and signal-dependent pre-mRNA splicing in the ...


    pub_type: 评论,杂志文章,评审


    authors: Meshorer E,Misteli T

    更新日期:2005-08-12 00:00:00

  • Lineage tracing.

    abstract::Lineage tracing is the identification of all progeny of a single cell. Although its origins date back to developmental biology of invertebrates in the 19(th) century, lineage tracing is now an essential tool for studying stem cell properties in adult mammalian tissues. Lineage tracing provides a powerful means of unde...


    pub_type: 历史文章,杂志文章


    authors: Kretzschmar K,Watt FM

    更新日期:2012-01-20 00:00:00

  • Dual Functions of a Rubisco Activase in Metabolic Repair and Recruitment to Carboxysomes.

    abstract::Rubisco, the key enzyme of CO2 fixation in photosynthesis, is prone to inactivation by inhibitory sugar phosphates. Inhibited Rubisco undergoes conformational repair by the hexameric AAA+ chaperone Rubisco activase (Rca) in a process that is not well understood. Here, we performed a structural and mechanistic analysis...


    pub_type: 杂志文章


    authors: Flecken M,Wang H,Popilka L,Hartl FU,Bracher A,Hayer-Hartl M

    更新日期:2020-10-15 00:00:00

  • The kinky propulsion of Spiroplasma.

    abstract::Bacteria have evolved many different means of generating movement. In this issue of Cell, Shaevitz et al. (2005) describe the swimming movement of a helical bacterium called Spiroplasma. They discover that Spiroplasma propels itself by generating two temporally distinct kinks that travel the length of the bacterium. T...


    pub_type: 评论,杂志文章,评审


    authors: Wolgemuth CW,Charon NW

    更新日期:2005-09-23 00:00:00

  • Spatially restricted expression of pipe in the Drosophila egg chamber defines embryonic dorsal-ventral polarity.

    abstract::Expression of pipe in the somatic tissue of the Drosophila ovary is required for the formation of embryonic dorsal-ventral polarity. pipe, which encodes an enzyme similar to the glycosaminoglycan-modifying enzyme heparan sulfate 2-O-sulfotransferase, is expressed in a spatially restricted domain of follicle cells on t...


    pub_type: 杂志文章


    authors: Sen J,Goltz JS,Stevens L,Stein D

    更新日期:1998-11-13 00:00:00

  • Forward transport. 14-3-3 binding overcomes retention in endoplasmic reticulum by dibasic signals.

    abstract::Proteins with dibasic retention motifs are subject to retrograde transport to endoplasmic reticulum (ER) by COPI-coated vesicles. As forward transport requires escape from ER retention, general release mechanisms have been expected. Here, KCNK3 potassium channels are shown to bear two cytoplasmic trafficking motifs: a...


    pub_type: 杂志文章


    authors: O'Kelly I,Butler MH,Zilberberg N,Goldstein SA

    更新日期:2002-11-15 00:00:00

  • Molecular and functional profiling of memory CD8 T cell differentiation.

    abstract::How and when memory T cells form during an immune response are long-standing questions. To better understand memory CD8 T cell development, a time course of gene expression and functional changes in antigen-specific T cells during viral infection was evaluated. The expression of many genes continued to change after vi...


    pub_type: 杂志文章


    authors: Kaech SM,Hemby S,Kersh E,Ahmed R

    更新日期:2002-12-13 00:00:00

  • Gradients of the Drosophila Chinmo BTB-zinc finger protein govern neuronal temporal identity.

    abstract::Many neural progenitors, including Drosophila mushroom body (MB) and projection neuron (PN) neuroblasts, sequentially give rise to different subtypes of neurons throughout development. We identified a novel BTB-zinc finger protein, named Chinmo (Chronologically inappropriate morphogenesis), that governs neuronal tempo...


    pub_type: 杂志文章


    authors: Zhu S,Lin S,Kao CF,Awasaki T,Chiang AS,Lee T

    更新日期:2006-10-20 00:00:00

  • Repression of heat shock transcription factor HSF1 activation by HSP90 (HSP90 complex) that forms a stress-sensitive complex with HSF1.

    abstract::Heat shock and other proteotoxic stresses cause accumulation of nonnative proteins that trigger activation of heat shock protein (Hsp) genes. A chaperone/Hsp functioning as repressor of heat shock transcription factor (HSF) could make activation of hsp genes dependent on protein unfolding. In a novel in vitro system, ...


    pub_type: 杂志文章


    authors: Zou J,Guo Y,Guettouche T,Smith DF,Voellmy R

    更新日期:1998-08-21 00:00:00

  • Protein disulfide isomerase acts as a redox-dependent chaperone to unfold cholera toxin.

    abstract::Cholera toxin is assembled from two subunits in the periplasm of Vibrio cholerae and disassembled in the analogous compartment of target cells, the lumen of the endoplasmic reticulum (ER), before a fragment of it, the A1 chain, is transported into the cytosol. We show that protein disulfide isomerase (PDI) in the ER l...


    pub_type: 杂志文章


    authors: Tsai B,Rodighiero C,Lencer WI,Rapoport TA

    更新日期:2001-03-23 00:00:00

  • Messenger RNA for the Ad2 DNA binding protein: DNA sequences encoding the first leader and heterogenity at the mRNA 5' end.

    abstract::During the early stage of Ad2 infection of human cells, RNA is transcribed from five separate transcription units. Early region II encodes the mRNA for a 72K single-stranded DNA binding protein (DBP) which functions in DNA replication. This report describes the structure of the first leader of the DBP mRNA and the fla...


    pub_type: 杂志文章


    authors: Baker CC,Herisse J,Courtois G,Galibert F,Ziff E

    更新日期:1979-10-01 00:00:00

  • Endocytosis Inhibition in Humans to Improve Responses to ADCC-Mediating Antibodies.

    abstract::A safe and controlled manipulation of endocytosis in vivo may have disruptive therapeutic potential. Here, we demonstrate that the anti-emetic/anti-psychotic prochlorperazine can be repurposed to reversibly inhibit the in vivo endocytosis of membrane proteins targeted by therapeutic monoclonal antibodies, as directly ...


    pub_type: 杂志文章


    authors: Chew HY,De Lima PO,Gonzalez Cruz JL,Banushi B,Echejoh G,Hu L,Joseph SR,Lum B,Rae J,O'Donnell JS,Merida de Long L,Okano S,King B,Barry R,Moi D,Mazzieri R,Thomas R,Souza-Fonseca-Guimaraes F,Foote M,McCluskey A,Robin

    更新日期:2020-03-05 00:00:00

  • Tumor promoter-induced changes in the permeability of epithelial cell tight junctions.

    abstract::Treatment of the kidney epithelial cell line MDCK with the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) induces a large increase in the permeability of tight junctions within 2-4 hr. This change in transepithelial permeability is accompanied by alterations in cell morphology that include the opening of ti...


    pub_type: 杂志文章


    authors: Ojakian GK

    更新日期:1981-01-01 00:00:00

  • ATR-X syndrome protein targets tandem repeats and influences allele-specific expression in a size-dependent manner.

    abstract::ATRX is an X-linked gene of the SWI/SNF family, mutations in which cause syndromal mental retardation and downregulation of α-globin expression. Here we show that ATRX binds to tandem repeat (TR) sequences in both telomeres and euchromatin. Genes associated with these TRs can be dysregulated when ATRX is mutated, and ...


    pub_type: 杂志文章


    authors: Law MJ,Lower KM,Voon HP,Hughes JR,Garrick D,Viprakasit V,Mitson M,De Gobbi M,Marra M,Morris A,Abbott A,Wilder SP,Taylor S,Santos GM,Cross J,Ayyub H,Jones S,Ragoussis J,Rhodes D,Dunham I,Higgs DR,Gibbons RJ

    更新日期:2010-10-29 00:00:00

  • Organoid models of human and mouse ductal pancreatic cancer.

    abstract::Pancreatic cancer is one of the most lethal malignancies due to its late diagnosis and limited response to treatment. Tractable methods to identify and interrogate pathways involved in pancreatic tumorigenesis are urgently needed. We established organoid models from normal and neoplastic murine and human pancreas tiss...


    pub_type: 杂志文章


    authors: Boj SF,Hwang CI,Baker LA,Chio II,Engle DD,Corbo V,Jager M,Ponz-Sarvise M,Tiriac H,Spector MS,Gracanin A,Oni T,Yu KH,van Boxtel R,Huch M,Rivera KD,Wilson JP,Feigin ME,Öhlund D,Handly-Santana A,Ardito-Abraham CM,L

    更新日期:2015-01-15 00:00:00

  • Reasons scientists avoid thinking about ethics.

    abstract::Science is a powerful force for change in modern society. As the professionals at its helm, scientists have a unique responsibility to shepherd that change with thoughtful advocacy of their research and careful ethical scrutiny of their own behavior. ...


    pub_type: 杂志文章


    authors: Wolpe PR

    更新日期:2006-06-16 00:00:00

  • Transcription termination within the E1A gene of adenovirus induced by insertion of the mouse beta-major globin terminator element.

    abstract::In induced erythroleukemia cells, transcription of the beta-globin gene terminates in a region 600-1500 nucleotides downstream of the poly(A) site. To determine whether this region of the mouse DNA functions to terminate transcription when moved to another genomic site, portions of the putative termination region have...


    pub_type: 杂志文章


    authors: Falck-Pedersen E,Logan J,Shenk T,Darnell JE Jr

    更新日期:1985-04-01 00:00:00

  • Correct integration of retroviral DNA in vitro.

    abstract::We have developed a cell-free system for studying the integration of retroviral DNA. In our assay, amber mutations in a bacteriophage lambda genome that serves as the target for integration are suppressed by integration of an MLV derivative that carries the E. coli supF gene. The structure of the reaction products is ...


    pub_type: 杂志文章


    authors: Brown PO,Bowerman B,Varmus HE,Bishop JM

    更新日期:1987-05-08 00:00:00

  • A novel octamer binding transcription factor is differentially expressed in mouse embryonic cells.

    abstract::We have identified a novel octamer binding factor (Oct-3) in P19 embryonal carcinoma cells. Oct-3, which recognizes the typical octamer motif (ATTTGCAT) as well as the AT-rich sequence TTAAAATTCA, is present in P19 stem cells but disappears when the cells are induced to differentiate by retinoic acid (RA). Cloned cDNA...


    pub_type: 杂志文章


    authors: Okamoto K,Okazawa H,Okuda A,Sakai M,Muramatsu M,Hamada H

    更新日期:1990-02-09 00:00:00

  • Coordinated dual cleavages induced by the proteasome regulator PA28 lead to dominant MHC ligands.

    abstract::The eukaryotic 20S proteasome is known to associate with the IFN gamma-inducible regulator PA28. We analyzed the kinetics of product generation by 20S proteasomes with and without PA28. In the absence of PA28, the 20S proteasome rapidly generates peptides that have been cleaved only once, while internal fragments accu...


    pub_type: 杂志文章


    authors: Dick TP,Ruppert T,Groettrup M,Kloetzel PM,Kuehn L,Koszinowski UH,Stevanović S,Schild H,Rammensee HG

    更新日期:1996-07-26 00:00:00

  • Topology and regulation of the human eIF4A/4G/4H helicase complex in translation initiation.

    abstract::The RNA helicase eIF4A plays a key role in unwinding of mRNA and scanning during translation initiation. Free eIF4A is a poor helicase and requires the accessory proteins eIF4G and eIF4H. However, the structure of the helicase complex and the mechanisms of stimulation of eIF4A activity have remained elusive. Here we r...


    pub_type: 杂志文章


    authors: Marintchev A,Edmonds KA,Marintcheva B,Hendrickson E,Oberer M,Suzuki C,Herdy B,Sonenberg N,Wagner G

    更新日期:2009-02-06 00:00:00

  • The BELL1 gene encodes a homeodomain protein involved in pattern formation in the Arabidopsis ovule primordium.

    abstract::Ovule development in Arabidopsis involves the formation of three morphologically defined proximal-distal pattern elements. Integuments arise from the central pattern element. Analysis of Bell 1 (Bel 1) mutant ovules indicated that BEL1 was required for integument development. Cloning of the BEL1 locus reveals that it ...


    pub_type: 杂志文章


    authors: Reiser L,Modrusan Z,Margossian L,Samach A,Ohad N,Haughn GW,Fischer RL

    更新日期:1995-12-01 00:00:00