Editors' Choice

Science  20 May 2005:
Vol. 308, Issue 5725, pp. 1088

    From Walkabout to Wanderlust

    Cells of the immune system are highly motile and use chemotaxis in navigating to and within different regions of the body. Communication between B cells and T cells is needed for antibody production and in the deployment of armed T cells to sites of infection. During development, immature immune cells must also find their way from their site of origin toward peripheral lymphoid organs.

    Using two-photon microscopy of lymph nodes, Okada et al. followed the fate of antigen-specific B cells. After activation, the cells within the follicular B cell zone awoke from a relatively sluggish, random motion and began to steer a steady course toward the neighboring region of the lymph node containing T cells. This process depended on the surface chemokine receptor CCR7, linking the gradient of the chemokine CCL21 within the follicle to the directional behavior. Once inside the T cell zone, B cells coupled with T cell partners in a multidirectional dance, with the B cells appearing to take the lead.

    In a study of developing T cells within the thymus, Witt et al. observed that thymocytes located within the cortical region altered their behavior after they had undergone positive selection. Similarly to follicular B cells, selected thymocytes switched from a random walk to directed migration toward the thymic medulla, through which they transit as they exit the thymus. Again, this suggests that long-distance cues induce the urge to travel in newly selected T cells. — SJS

    PLoS Biol. 3, e150; e160 (2005).


    Up From the Depths

    Recent geological and chemical evidence supports the conclusion that in the distant past, Earth's oceans were repeatedly stratified, so that an anoxic layer formed at depth, as in the Black Sea of today. During these periods, bacterial metabolism would have used sulfate (instead of oxygen) as an electron acceptor, and the deep oceans would have become enriched in hydrogen sulfide as a consequence.

    Kump et al. show that the upward flux of the accumulated hydrogen sulfide would have been quenched by the mixing of atmospheric oxygen into the surface of the oceans. They go on to infer that at times when the atmospheric oxygen level was low, large-scale upwelling of hydrogen sulfide gas might have taken over and that, in extreme cases, this could have resulted in the release of significant amounts of this toxic gas into the atmosphere. Biomarkers indicative of a high abundance of nonoxygenic photosynthetic green sulfur bacteria have been found, corresponding to the times of several mass extinctions and most recently for the end-Permian extinction (see Grice et al., Reports, 4 February 2005, p. 706), which is broadly associated with low oxygen levels and extensive ocean anoxia. — BH

    Geology 33, 397 (2005).


    House of Triangles

    Atomic clusters often adopt cage-like geometries with triangular faces, such as the tetrahedron, octahedron, and icosahedron. Goicoechea and Sevov have extended this series by constructing a germanium cluster composed of 32 triangles. The Ge18 ellipsoid has approximate threefold symmetry and a charge of 4, and was crystallized with four charge-balancing potassium ions that were sequestered inside cryptand ligands. The cluster encapsulates two palladium atoms, which appear to stabilize the large cage from within by overlapping with the Ge orbitals. The synthesis fuses the two cluster halves together from a solution of K4Ge9 and tetrakis(triphenylphosphine) palladium precursors. Although a similar geometry has been seen in extended solid lattices, mass spectrometry confirmed that these structures are stable as discrete species in solution. — JSY

    J. Am. Chem. Soc. 10.1021/ja051224q (2005).


    Staying Hydrated

    The peptide vasopressin (antidiuretic hormone) is critical for maintaining fluid homeostasis. Its receptor, V2R, is located at the surface of epithelial cells lining the kidney's collecting duct. Receptor activation increases water permeability through aquaporin, leading to the retention of water. Mutation of an arginine residue to histidine at position 137 of V2R blocks receptor activation, resulting in nephrogenic diabetes insipidus, in which patients suffer from severe dehydration due to excessive water excretion. The critical arginine is located within a motif that is highly conserved in the family of G protein-coupled receptors.

    Feldman et al. find that if the arginine is mutated to either cysteine or leucine, the opposite condition occurs—excessive water retention—and they refer to this condition as nephrogenic syndrome of inappropriate antidiuresis. The mutations were identified in two infants who displayed the abnormal water overload characteristic of hyperactivated V2R, even though both patients lacked detectable vasopressin. It remains to be determined how mutations at the same position either activate or inactivate the receptor, causing genetic disorders of opposite character. — LDC

    N. Engl. J. Med. 352, 1884 (2005).


    Feeling Dehydrated

    Bacteria monitor their environment and change their behavior to exploit that environment most effectively. Wang et al. have discovered an unanticipated player that bacteria use to sense environmental wetness: the bacterial flagellum. One key ingredient for continued growth is a source of water; at a hydrated surface, bacteria form large colonies that swarm across the surface via flagella-driven motility. Mutants in the bacterial chemotaxis signaling pathway exhibit fewer and shorter flagella when grown on a surface and are less hydrated than wildtype cells. It seems that the flagella sense external wetness, and when external hydration is limiting, the flagella inhibit their own growth by blocking the secretion of flagellin subunits and the export of the transcriptional inhibitor FlgM, thereby switching off the synthesis of further flagellum components. The specialized secretion systems responsible for the export and assembly of flagella and for the secretion of bacterial virulence factors are jointly regulated by this sensing system. — SMH

    EMBO J. 10.1038/sj.emboj.7600668 (2005).


    DNA as a Chiral Catalyst

    Chemists have long explored the use of biocatalysts such as proteins and RNA in their syntheses; the handedness of these molecules is particularly useful for the selective synthesis of individual enantiomers (the two mirror-image forms of chiral molecules).

    Roelfes and Feringa show that inter-calation of a suitable catalyst into DNA enables enantioselective synthesis. Because the catalyst itself is nonchiral, the chirality of the DNA is responsible for the chiral selectivity. Through judicious choice of catalyst, the authors can even prepare both enantiomers of the product. The catalyst is noncovalently bound to the DNA, allowing the system to be optimized and adapted rapidly for new reactions. Furthermore, the product can be separated easily from the reaction mixture. — JFU

    Angew. Chem. Int. Ed. 10.1002/ange.200500298 (2005).

  7. STKE

    Methylation Outside the Nucleus

    Ezh2 is a member of the polycomb group of proteins and functions in development by catalyzing the methylation of lysine residues on histone proteins, thereby causing changes in gene expression. However, Ezh2 exists in the cytoplasm as well as the nucleus, and Su et al. have explored whether the enzyme might have functions apart from its role in modifying chromatin structure. Ezh2 has been reported to associate with the guanine nucleotide exchange factor Vav1, which is an important component of T cell signaling and mediator of changes in actin polymerization in response to stimulation of the T cell receptor (TCR). T cells lacking Ezh2 were defective in TCR-induced actin polymerization and showed an impaired proliferative response. Similarly, fibroblasts lacking Ezh2 showed decreased actin polymerization in response to platelet-derived growth factor, and this deficiency could be rescued by expressing a cytoplasmically localized form of Ezh2. The methylation target of Ezh2 is not known but appears to lie between TCR activation and activation of the guanosine triphosphate Cdc42; Vav1, though, appears not be modified by Ezh2. These findings indicate that posttranslational modification by methylation has key regulatory roles outside of the nucleus, with implications for immune responses to the TCR and cancer biology, where increased expression of Ezh2 in cancer cells is associated with increased metastatic capacity. — LBR

    Cell 121, 426 (2005).

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