Science's STKEPub Date : 2002-06-25DOI: 10.1126/scisignal.1382002tw225
{"title":"Building Up and Tearing Down","authors":"","doi":"10.1126/scisignal.1382002tw225","DOIUrl":"https://doi.org/10.1126/scisignal.1382002tw225","url":null,"abstract":"Hormone induction can stop very rapidly once the hormone is removed. What is the mechanism for this rapid cessation of transcription? Freeman and Yamamoto (p. 2232) show that molecular chaperones can disassemble the large multisubunit complexes that form on promoters and that induce gene expression. The authors used chimeric constructs to increase the local concentration of the chaperones in vivo and showed that when the chaperone p23 is localized to a promoter region, transcription is down-regulated. Hence, chaperones may play dual roles in the assembly and disassembly of transcription complexes. B. C. Freeman, K. R. Yamamoto, Disassembly of transcriptional regulatory complexes by molecular chaperones.Science 296, 2232-2235 (2002). [Abstract] [Full Text]","PeriodicalId":21619,"journal":{"name":"Science's STKE","volume":"1 1","pages":"TW225 - tw225"},"PeriodicalIF":0.0,"publicationDate":"2002-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86442629","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Science's STKEPub Date : 2002-06-18DOI: 10.1126/scisignal.1372002tw218
{"title":"One Tyrosine Short","authors":"","doi":"10.1126/scisignal.1372002tw218","DOIUrl":"https://doi.org/10.1126/scisignal.1372002tw218","url":null,"abstract":"LAT is an intracellular adaptor protein that becomes phosphorylated on multiple tyrosine residues after T cell receptor activation. Agaudo et al. and Sommers et al. report that a single tyrosine residue in LAT, which couples to the downstream signaling molecule phospholipase C-γ1, plays a crucial role in maintaining T cell homeostasis, regulating both early and late T cell development and differentiation. Replacement of endogenous LAT in mice with a form in which Tyr136 was mutated to Phe caused a partial block in early T cell development. However, over time, the mice developed a fatal lymphoproliferative disorder featuring an overabundance of a particular Th2-type cell. One consequence of this paradoxical phenotype was an autoimmune response. The analyses suggest that, although a single LAT residue may have a positive function during early T cell development, it may negatively regulate signaling pathways later on during T cell selection and differentiation of Th2 effector cells. E. Aguado, S. Richelme, S. Nuñez-Cruz, A. Miazek, A.-M. Mura, M. Richelme, X.-J. Guo, D. Sainty, H.-T. He, B. Malissen, M. Malissen, Induction of T helper type 2 immunity by a point mutation in the LAT adaptor. Science 296, 2036-2040 (2002). [Abstract] [Full Text] C. L. Sommers, C.-S. Park, J. Lee, C. Feng, C. L. Fuller, A. Grinberg, J. A. Hildebrand, E. Lacaná, R. K. Menon, E. W. Shores, L. E. Samelson, P. E. Love, A LAT mutation that inhibits T cell development yet induces lymphoproliferation. Science 296, 2040-2043 (2002). [Abstract] [Full Text]","PeriodicalId":21619,"journal":{"name":"Science's STKE","volume":"53 1","pages":"TW218 - tw218"},"PeriodicalIF":0.0,"publicationDate":"2002-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79179907","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Science's STKEPub Date : 2002-06-11DOI: 10.1126/scisignal.1362002tw210
{"title":"Animated Immunity","authors":"","doi":"10.1126/scisignal.1362002tw210","DOIUrl":"https://doi.org/10.1126/scisignal.1362002tw210","url":null,"abstract":"Our current understanding of the complex cellular interactions required for immune responses has come largely from in vitro manipulation or from snapshots of events within fixed tissues. Three reports now describe real-time analysis of immune cell responses within living tissues (see the Perspective by von Adrian). Using two-photon technology to compare migration of T and B cells within organized lymphoid tissue, Miller et al. observed that T cells roam considerably further and at faster rates than B cells. This explorative behavior shifted toward focused clustering upon inclusion of antigen. Stoll et al. used modified single-photon confocal imaging to investigate interactions of naïve T cells with antigen on dendritic cell (DC) in lymph nodes. Extended periods of connection, with the formation of immune synapses and eventual departure of activated T cells, were observed in the presence of antigen-loaded DCs. Bousso et al. used two-photon imaging to study thymocyte interactions with thymic stromal cells in a reaggregated thymic organ culture. Recognition events that resulted in positive selection of thymocytes promoted thymocyte motility and increased the duration of thymocyte-thymic stromal cell contacts. U. H. von Andrian, T cell activation in six dimensions. Science 296, 1815-1817 (2002). [Summary] [Full Text] M. J. Miller, S. H. Wei, I. Parker, M. D. Cahalan, Two-photon imaging of lymphocyte motility and antigen response in intact lymph node. Science 296, 1869-1873 (2002). [Abstract] [Full Text] S. Stoll, J. Delon, T. M. Brotz, R. N. Germain, Dynamic imaging of T cell-dendritic cell interactions in lymph nodes. Science 296, 1873-1876 (2002). [Abstract] [Full Text] P. Bousso, N. R. Bhakta, R. S. Lewis, E. Robey, Dynamics of thymocyte-stromal cell interactions visualized by two-photon microscopy. Science 296, 1876-1880 (2002). [Abstract] [Full Text]","PeriodicalId":21619,"journal":{"name":"Science's STKE","volume":"129 1","pages":"TW210 - tw210"},"PeriodicalIF":0.0,"publicationDate":"2002-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74193293","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Science's STKEPub Date : 2002-06-11DOI: 10.1126/scisignal.1362002tw205
{"title":"Assessing CNS Axon Regeneration","authors":"","doi":"10.1126/scisignal.1362002tw205","DOIUrl":"https://doi.org/10.1126/scisignal.1362002tw205","url":null,"abstract":"Neurons of the central nervous system (CNS) are much less able to repair themselves after damage than are neurons of the peripheral nervous system. The causes might lie with the differences in environment and type of surrounding glia, or with the neurons themselves. Goldberg et al. (see the Perspective by McKerracher and Ellezam) have isolated retinal ganglion cells, which form part of the CNS, from the rat to study their ability to regenerate axons. RGCs isolated from embryonic rats showed a much greater capability for axon regeneration than did RGCs from early postnatal rats. The diminishing capacity for axonal regeneration correlated with developmental times at which the RGC axons would normally have reached their targets and switched from axonal growth to dendrite elaboration. The switch in growth mode was not related to intrinsic cell age but rather arose from signals from neighboring retinal cells. J. L. Goldberg, M. P. Klassen, Y. Hua, B. A. Barres, Amacrine-signaled loss of intrinsic axon growth ability by retinal ganglion cells. Science 296, 1860-1864 (2002). [Abstract] [Full Text] L. McKerracher, B. Ellezam, Putting the brakes on regeneration. Science 296, 1819-1820 (2002). [Summary] [Full Text]","PeriodicalId":21619,"journal":{"name":"Science's STKE","volume":"51 1","pages":"TW205 - tw205"},"PeriodicalIF":0.0,"publicationDate":"2002-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84688308","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Science's STKEPub Date : 2002-06-11DOI: 10.1126/scisignal.1362002tw211
{"title":"Gradient Amplification","authors":"","doi":"10.1126/scisignal.1362002tw211","DOIUrl":"https://doi.org/10.1126/scisignal.1362002tw211","url":null,"abstract":"During chemotaxis, cells can sense remarkably shallow gradients in the concentration of chemoattractants that may differ by only a few percent from one end of the cell to the other. Chemoattractant receptors and their associated G proteins appear to remain evenly distributed in responding cells. However, some signaling proteins do accumulate at the leading edge of migrating cells in a manner dependent on their pleckstrin homology (PH) domains. PH domains bind to 3-phosphoinositides, so Funamoto et al. and Iijima and Devreotes have now used Dictyostelium cells to assess the distribution of phosphatidylinositol 3-kinase (PI3K) and the phosphatidylinositol-3-phosphatase PTEN, which control synthesis and degradation of the 3-phosphoinositides. Funamoto et al. found that PI3Ks tagged with green fluorescent protein were localized to the leading edge of cells exposed to a chemoattractant gradient. Both groups report that fluorescently tagged PTEN undergoes a reciprocal localization: it is lost from the leading edge and increases in concentration at the sides and rear of the cell. Loss of PTEN caused prolonged and broader spatial distribution of PH domain binding across the leading edge of the cell. Iijima and Devreotes showed that a putative binding domain for phophatidylinositol 4,5-bisphosphate [PI(4,5)P2] on PTEN is required for its localization and function. They propose that loss of PI(4,5)P2 as it becomes phosphorylated by PI3K at the leading edge of the cell may contribute to an amplification loop that leads to loss of PTEN from the membrane. The initial signal that leads to differential localization of PI3K is still not known, but localization of PI3K and PTEN and feedback regulation of PTEN appear to contribute to amplification of the chemoattractant gradient. S. Funamoto, R. Meili, S. Lee, L. Parry, R. A. Firtel, Spatial and temporal regulation of 3-phosphoinositides by PI 3-kinase and PTEN mediates chemotaxis. Cell 109, 611-623 (2002). [Online Journal] M. Iijima, P. Devreotes, Tumor suppressor PTEN mediates sensing of chemoattractant gradients. Cell 109, 599-610 (2002). [Online Journal]","PeriodicalId":21619,"journal":{"name":"Science's STKE","volume":"106 1","pages":"TW211 - tw211"},"PeriodicalIF":0.0,"publicationDate":"2002-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77814782","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Science's STKEPub Date : 2002-05-07DOI: 10.1126/scisignal.1312002tw171
{"title":"Sparsely Connected Hubs in Protein Networks","authors":"","doi":"10.1126/scisignal.1312002tw171","DOIUrl":"https://doi.org/10.1126/scisignal.1312002tw171","url":null,"abstract":"Genomic and proteomic analyses, combined with accumulated knowledge of cell signaling pathways, are exposing characteristics of the regulatory networks that control physiology. In fact, there is now sufficient detail so that the properties of the networks themselves can be described and analyzed. Maslov and Sneppen examined the protein interaction network described by a systematic screen of yeast protein interactions by the two-hybrid method and also a network of yeast proteins whose regulatory interactions have been genetically defined. In both cases, a relatively small set of proteins are highly connected to other proteins, but these highly connected proteins are primarily connected to proteins with sparse connectivity, not to other proteins that are highly connected. This suppression of interaction of the highly connected nodes in the network has implications for specificity and cross talk in the signaling mechanisms. The authors note that, for reasons not yet clear, the organization of the protein networks is similar to that for interconnection of internet service providers. S. Maslov, K. Sneppen, Specificity and stability in topology of protein networks. Science 296, 910-913 (2002). [Abstract] [Full Text]","PeriodicalId":21619,"journal":{"name":"Science's STKE","volume":"194 1","pages":"tw171 - tw171"},"PeriodicalIF":0.0,"publicationDate":"2002-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72801504","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Science's STKEPub Date : 2002-05-07DOI: 10.1126/scisignal.1312002tw164
Joel Achenbach
{"title":"Who's Driving?","authors":"Joel Achenbach","doi":"10.1126/scisignal.1312002tw164","DOIUrl":"https://doi.org/10.1126/scisignal.1312002tw164","url":null,"abstract":"Kinesins are molecular motors that transport cargo such as proteins and membrane vesicles around the cell. In the case of a polarized cell like the neuron, kinesins ensure that cargo destined for axons or dendrites gets properly directed. However, just what \"steers\" these motors in the right direction is not clear. Setou et al. report that a binding protein of GluR2, one of the subunits of the dendritic α-amino-3-hydroxy-5-methylisoxazole-4-proprionate (AMPA) receptor, binds to the cargo-binding domain of the kinesin heavy chain. This binding protein, called glutamate-receptor-interacting protein (GRIP), colocalized with kinesin in dendritic shafts and soma of brain neurons. Kinesin also coimmunoprecipitated with GRIP and with GluR2 from dendrite-enriched subcellular brain fractions. Expression of the kinesin-binding domain of GRIP delocalized endogenous kinesin in somatodendritic regions but not in axons. A kinesin dominant negative mutant containing only the GRIP binding site reduced GRIP and GluR2 localization in synapses. Another scaffolding protein called c-Jun amino-terminal-kinase-interacting protein-1 (JIP) is known to bind to the kinesin light chain and is axon directed. Hence, traffic in neurons may be directed by categories of binding proteins that bring distinct motors and cargo together. M. Setou, D.-H. Seog, Y. Tanaka, Y. Kanai, Y. Takei, M. Kawagishi, N. Hirokawa, Glutamate-receptor-interacting protein GRIP directly steers kinesin to dendrites. Nature 417, 83-87 (2002). [Online Journal]","PeriodicalId":21619,"journal":{"name":"Science's STKE","volume":"1 1","pages":"tw164 - tw164"},"PeriodicalIF":0.0,"publicationDate":"2002-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77221327","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Science's STKEPub Date : 2002-05-07DOI: 10.1126/scisignal.1312002tw170
{"title":"Tackling the Link Between Stress and Alcohol","authors":"","doi":"10.1126/scisignal.1312002tw170","DOIUrl":"https://doi.org/10.1126/scisignal.1312002tw170","url":null,"abstract":"The chances of developing alcoholism throughout one's life are determined by a genetic predisposition and an individual's reaction to lifetime events, such a stress. The corticotropin-releasing hormone (CRH) system regulates endocrine responses to stress and mediates stress-related behavior. To better understand the molecular and cellular mechanism underlying stress-induced alcohol drinking Sillaber et al. created knockout mice lacking CRH1 receptors. Crhr1−/− mice did not differ from wild-type mice in their basal alcohol intake and preference. However, after repeated stress episodes, the knockout mice gradually increased their alcohol consumption and kept it elevated for the rest of their life. This change in drinking behavior was accompanied by enhanced protein levels of the NR2B subunit of the N-methyl-D-aspartate receptor. I. Sillaber, G. Rammes, S. Zimmermann, B. Mahal, W. Zieglgänsberger, W. Wurst, F. Holsboer, R. Spanagel, Enhanced and delayed stress-induced alcohol drinking in mice lacking functional CRH1 receptors. Science 296, 931-933 (2002). [Abstract] [Full Text]","PeriodicalId":21619,"journal":{"name":"Science's STKE","volume":"6 1","pages":"tw170 - tw170"},"PeriodicalIF":0.0,"publicationDate":"2002-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74946843","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Science's STKEPub Date : 2002-04-23DOI: 10.1126/scisignal.1292002tw149
{"title":"Rare Lineage","authors":"","doi":"10.1126/scisignal.1292002tw149","DOIUrl":"https://doi.org/10.1126/scisignal.1292002tw149","url":null,"abstract":"A small subset of T lymphocytes express markers characteristic of natural killer (NK) cells and has been shown to regulate adaptive immune responses. Compared with conventional T cells, the development of these NKT cells is poorly understood, although it is known that they are positively selected by major histocompatibility complex-like CD1 ligands within in the thymus. Benlagha et al. (see the Perspective by MacDonald) used tetramer staining to characterize NKT cells precursors in wild-type populations of thymocytes and to track their emigration from the thymus into peripheral tissues. The NK phenotype displayed by these cells actually occurred after these cells exited the thymus. More striking was a progression from expression of the cytokine interleukin-4 to interferon-γ, which may reflect distinct mechanisms of immune regulation mediated by these cells. K. Benlagha, T. Kyin, A. Beavis, L. Teyton, A. Bendelac, A thymic precursor to the NKT cell lineage. Science 296, 553-555 (2002). [Abstract] [Full Text] H. R. MacDonald, T before NK. Science 296, 481 (2002). [Summary] [Full Text]","PeriodicalId":21619,"journal":{"name":"Science's STKE","volume":"39 1","pages":"tw149 - tw149"},"PeriodicalIF":0.0,"publicationDate":"2002-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85020527","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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