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  • 1
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    A composition-dependent molecular clutch between T cell signaling condensates and actin (2019)
    eLife Sciences Publications
    Details
    Publication Date: 2022-05-26
    Description: © The Author(s), 2019. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Ditlev, J. A., Vega, A. R., Köster, D. V., Su, X., Tani, T., Lakoduk, A. M., Vale, R. D., Mayor, S., Jaqaman, K., & Rosen, M. K. A composition-dependent molecular clutch between T cell signaling condensates and actin. Elife, 8, (2019): e42695, doi:10.7554/eLife.42695.
    Description: During T cell activation, biomolecular condensates form at the immunological synapse (IS) through multivalency-driven phase separation of LAT, Grb2, Sos1, SLP-76, Nck, and WASP. These condensates move radially at the IS, traversing successive radially-oriented and concentric actin networks. To understand this movement, we biochemically reconstituted LAT condensates with actomyosin filaments. We found that basic regions of Nck and N-WASP/WASP promote association and co-movement of LAT condensates with actin, indicating conversion of weak individual affinities to high collective affinity upon phase separation. Condensates lacking these components were propelled differently, without strong actin adhesion. In cells, LAT condensates lost Nck as radial actin transitioned to the concentric network, and engineered condensates constitutively binding actin moved aberrantly. Our data show that Nck and WASP form a clutch between LAT condensates and actin in vitro and suggest that compositional changes may enable condensate movement by distinct actin networks in different regions of the IS. https://doi.org/10.7554/eLife.42695.001
    Description: We thank L Rice, J Hammer III, and our fellow HCIA Summer Institute scientists for stimulating discussions about this study. This work was supported by a Howard Hughes Medical Institute Collaborative Innovation Award, the Welch Foundation (I-1544 to MKR), a JC Bose Fellowship from the Department of Science and Technology, government of India (SM), a Margadarshi Fellowship from the Wellcome Trust – Department of Biotechnology, India Alliance (IA/M/15/1/502018 to SM), NIH (R01 GM100160 to TT) (R35 GM119619 to KJ), a CPRIT Recruitment Award (R1216 to KJ), and the UT Southwestern Endowed Scholars Program (KJ). Research in the Rosen lab is supported by the Howard Hughes Medical Institute. JAD was supported by a National Research Service Award F32 (F32 DK101188). ARV was supported by a CPRIT Training Grant (RP140110, PI: Michael White). DVK was supported by fellowships of the AXA Research Fund and the National Centre for Biological Sciences, Tata Institute for Fundamental Research. XS was supported by a Cancer Research Institute Irvington postdoctoral fellowship.
    Repository Name: Woods Hole Open Access Server
    Type: Article
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  • 2
    Electronic Resource
    Electronic Resource
    Distributions on rational function fields (1981)
    Springer
    Mathematische Annalen 256 (1981), S. 549-560 
    Details
    ISSN: 1432-1807
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mathematics
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01450548
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  • 3
    Electronic Resource
    Electronic Resource
    Controls on the chemical composition of groundwater from alluvial aquifers in the Wanaka and Wakatipu basins, Central Otago, New Zealand (1998)
    Springer
    Hydrogeology journal 6 (1998), S. 264-281 
    Details
    ISSN: 1435-0157
    Keywords: Key words New Zealand ; hydrochemistry ; groundwater quality ; metamorphic rocks ; unconsolidated sediments
    Source: Springer Online Journal Archives 1860-2000
    Topics: Geosciences
    Description / Table of Contents: Résumé Dans les aquifères alluviaux des bassins de Wakatipu et de Wanaka (Otago central, Nouvelle-Zélande), la composition chimique des eaux souterraines peut être résumée ainsi, en équivalents: Ca2+≫Mg2+≅Na+ 〉K+ pour les cations, et HCO3 –≫SO4 2-〉NO3 – et Cl– pour les anions. En équivalents, le rapport entre Ca2+ et HCO3 – est de l'ordre de 1; ces ions représentent plus de 80% des ions présents dans la solution. Cependant, une partie de ces eaux souterraines possède des teneurs plus élevées en Na+ et SO4 2-, ce qui traduit une origine différente. Les matériaux constituant les aquifères alluviaux de ces deux bassins proviennent de l'érosion et de l'altération des schistes métamorphiques d'Otago (schistes gris et verts). La calcite est un minéral accessoire présent pour moins de 5% aussi bien dans les schistes gris que dans les verts. La cartographie géologique des deux bassins montre que la dissolution de la calcite des schistes est le seul mécanisme possible pour donner à l'eau souterraine une composition chimique aussi constante et caractérisée par un rapport 1 entre Ca2+ et HCO3 –. L'eau souterraine possédant les plus fortes teneurs en Na+ et en SO4 2- est présente près des zones où affleurent les schistes; cette eau souterraine est une eau d'origine plus profonde et probablement plus ancienne, provenant du substratum. Les concentrations anormalement fortes en K+ dans le bassin de Wakatipu et les concentrations élevées en NO3 – dans celui de Wanaka ne peuvent pas être attribuées à une interaction avec les roches du substratum; de telles teneurs correspondent probablement à l'influence anthropique sur la composition de l'eau souterraine.
    Abstract: Resumen Las aguas subterráneas en los acuíferos aluviales de las cuencas de Wakatipu y Wanaka, en Central Otago, Nueva Zelanda, tienen una composición química de manera que, expresándolos en términos de en equivalentes, los iones se pueden ordenar como Ca2+≫Mg2+≅Na+〉K+ para los cationes, y HCO3 –≫SO4 2-〉NO3 –≅Cl–para los aniones. Ca2+ y HCO3 – presentan una equivalencia 1 : 1, y entre los dos suponen más del 80% de los iones en disolución. Sin embargo, algunas aguas subterráneas presentan cantidades mayores de Na+ y SO4 2-, lo que refleja una procedencia diferente. El material rocoso de los acuíferos aluviales en ambas cuencas procede de la erosión y la alteración del Esquisto de Otago (esquistos grises y verdes). La calcita es un mineral presente en ambos esquistos, aunque con proporciones menores del 5%. Los mapas geológicos de ambas cuencas indican que la disolución de calcita procedente de los esquistos es el único mecanismo probable para producir unas aguas subterráneas con una composición tan constante de carbonato cálcico. Aguas subterráneas con mayores contenidos de Na+ y SO4 2- tienen lugar en zonas donde los esquistos afloran en superficie, por lo que estas aguas son más profundas y más viejas y provienen de circulación profunda, por la base del acuífero. Valores anormalmente altos de K+ en la cuenca de Wakatipu y de NO3 – en la de Wanaka no pueden justificarse por la interacción con los materiales de la base del acuífero, por lo que estas concentraciones están probablemente influenciadas por fuentes antrópicas.
    Notes: Abstract  Groundwater in alluvial aquifers of the Wakatipu and Wanaka basins, Central Otago, New Zealand, has a composition expressed in equivalent units of Ca2+≫Mg2+≅Na+〉K+ for cations, and HCO3 –≫SO4 2-〉NO3 –≅Cl– for anions. Ca2+ and HCO3 – occur on a 1 : 1 equivalent basis and account for 〉80% of the ions in solution. However, some groundwater has increased proportions of Na+ and SO4 2-, reflecting a different source for this water. The rock material of the alluvial aquifers of both basins is derived from the erosion and weathering of metamorphic Otago Schist (grey and green schists). Calcite is an accessory mineral in both the grey and green schists at 〈5% of the rock. Geological mapping of both basins indicates that dissolution of calcite from the schist is the only likely mechanism for producing groundwater with such a constant composition dominated by Ca2+ and HCO3 – on a 1 : 1 equivalent basis. Groundwater with higher proportions of Na+ and SO4 2- occurs near areas where the schist crops out at the surface, and this groundwater represents deeper and possibly older water derived from basement fluids. Anomalously high K+ in the Wakatipu basin and high NO3 – concentrations in the Wanaka basin cannot be accounted for by interaction with basement lithologies, and these concentrations probably represent the influence of anthropogenic sources on groundwater composition.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s100400050150
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  • 4
    Electronic Resource
    Electronic Resource
    The asymptotic behavior of the class group of a function field over a finite field (1973)
    Springer
    Archiv der Mathematik 24 (1973), S. 287-296 
    Details
    ISSN: 1420-8938
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mathematics
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01228212
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  • 5
    Electronic Resource
    Electronic Resource
    Some remarks on thep-rank of an algebraic curve (1983)
    Springer
    Archiv der Mathematik 41 (1983), S. 143-146 
    Details
    ISSN: 1420-8938
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mathematics
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01196870
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  • 6
    Electronic Resource
    Electronic Resource
    On the rank of an elliptic surface (1998)
    Springer
    Inventiones mathematicae 133 (1998), S. 43-67 
    Details
    ISSN: 1432-1297
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mathematics
    Notes: Abstract. Nagao has recently given a conjectural limit formula for the rank of an elliptic surface E in terms of a weighted average of fibral Frobenius trace values. We show that Tate's conjecture on the order of vanishing of L 2(E,s) essentially implies Nagao's formula; in particular, we prove Nagao's formula for rational elliptic surfaces. In the case that E is a twist, we reduce Nagao's and Tate's conjectures to the case of products of curves, and we verify the conjectures for many new classes of elliptic surfaces of Kodaira dimension 0 and 1.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002220050238
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  • 7
    Electronic Resource
    Electronic Resource
    NMR detection of side chain–side chain hydrogen bonding interactions in 13C/15N-labeled proteins (2000)
    Springer
    Journal of biomolecular NMR 17 (2000), S. 305-310 
    Details
    ISSN: 1573-5001
    Keywords: FKBP12 ; NMR detection ; sensitivity enhancement ; side chain–side chain hydrogen bonds
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract We describe the direct observation of side chain–side chain hydrogen bonding interactions in proteins with sensitivity-enhanced NMR spectroscopy. Specifically, the remote correlation between the guanidinium nitrogen 15Nε of arginine 71, which serves as the hydrogen donor, and the acceptor carboxylate carbon 13CO2 γ of aspartate 100 in a 12 kDa protein, human FKBP12, is detected via the trans-hydrogen bond 3h J Nε CO2γ coupling by employing a novel HNCO-type experiment, soft CPD-HNCO. The 3h J Nε CO2γ coupling constant appears to be even smaller than the average value of backbone 3h J NC′ couplings, consistent with more extensive local dynamics in protein side chains. The identification of trans-hydrogen bond J-couplings between protein side chains should provide useful markers for monitoring hydrogen bonding interactions that contribute to the stability of protein folds, to alignments within enzyme active sites and to recognition events at macromolecular interfaces.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008390813387
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  • 8
    Electronic Resource
    Electronic Resource
    Detection of very weak side chain–main chain hydrogen bonding interactions in medium-size 13C/15N-labeled proteins by sensitivity-enhanced NMR spectroscopy (2000)
    Springer
    Journal of biomolecular NMR 17 (2000), S. 79-82 
    Details
    ISSN: 1573-5001
    Keywords: FKBP12 ; NMR detection ; sensitivity enhancement ; side chain–main chain hydrogen bonds
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract We describe the direct observation of very weak side chain–main chain hydrogen bonding interactions in medium-size 13C/15N-labeled proteins with sensitivity-enhanced NMR spectroscopy. Specifically, the remote correlation between the hydrogen acceptor side chain carboxylate carbon 13CO2 δ of glutamate 54 and the hydrogen donor backbone amide 15N of methionine 49 in a 12 kDa protein, human FKBP12, is detected via the trans-hydrogen bond 3h J NCO2δ coupling by employing a novel sensitivity-enhanced HNCO-type experiment, CPD-HNCO. The 3h J NCO2δ coupling constant appears to be even smaller than the average value of backbone 3h J NC′ couplings, consistent with more extensive local dynamics in protein side chains.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008373501591
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  • 9
    Electronic Resource
    Electronic Resource
    An (H)C(CO)NH-TOCSY pulse scheme for sequential assignment of protonated methyl groups in otherwise deuterated 15N, 13C-labeled proteins (1996)
    Springer
    Journal of biomolecular NMR 8 (1996), S. 351-356 
    Details
    ISSN: 1573-5001
    Keywords: (H)C(CO)NH-TOCSY ; Multidimensional NMR ; Deuteration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Summary A biosynthetic strategy has recently been developed for the production of 15N, 13C, 2H-labeled proteins using 1H3C-pyruvate as the sole carbon source and D2O as the solvent. The methyl groups of Ala, Val, Leu and Ile (γ2 only) remain highly protonated, while the remaining positions in the molecule are largely deuterated. An (H)C(CO)NH-TOCSY experiment is presented for the sequential assignment of the protonated methyl groups. A high-sensitivity spectrum is recorded on a 15N, 13C, 2H, 1H3C-labeled SH2 domain at 3°C (correlation time 18.8 ns), demonstrating the utility of the method for proteins in the 30–40 kDa molecular weight range.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00410333
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  • 10
    Electronic Resource
    Electronic Resource
    G protein-adrenergic interactions in the heart (1988)
    Springer
    Molecular and cellular biochemistry 82 (1988), S. 5-11 
    Details
    ISSN: 1573-4919
    Keywords: catecholamines ; cultured heart cells ; Purkinje fibers ; pertussis toxin ; lymphocytes ; beta receptors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Summary Guanine nucleotide binding proteins were examined for their influence in developmental and adaptive models of adrenergic actions in the heart. In primary cultures of rat cardiac myocytes, the positive chronotropic response to the alpha-agonist, phenylephrine, changes to negative when these cells are grown with and innervated by sympathetic nerves from the paravertebral chain. Innervated cells have significantly more G protein, as determined by the ADP-ribosylation reaction catalyzed by pertussis toxin, which is linked functionally to the negative chronotropic response. Adult canine Purkinje fibers that respond to phenylephrine with a decrease in automaticity are also linked biochemically and functionally to a G protein that serves as a pertussis toxin substrate. Fibers that increase in automaticity after exposure to phenylephrine, either under control conditions (a minority of fibers) or after prior exposure to pertussis toxin (a majority of fibers), have markedly reduced levels of G. A G protein was also shown to be important in the blunted adrenergic responsiveness that characterizes congestive heart failure in human subjects. In this model, the receptor complex is beta-adrenergic and the involved G protein is a cholera toxin substrate. Gs is reduced in the lymphocytes of patients with congestive heart failure and increases toward normal after successful therapy. These observations highlight the important roles that G proteins have in adrenergic actions of the heart both with respect developmental and adaptive changes.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00242509
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