Pub Date : 2002-06-25DOI: 10.1126/scisignal.1382002tw225
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]
{"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}
Pub Date : 2002-06-18DOI: 10.1126/scisignal.1372002tw218
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]
LAT是一种细胞内接头蛋白，在T细胞受体激活后，在多个酪氨酸残基上被磷酸化。Agaudo等人和Sommers等人报道LAT中单个酪氨酸残基与下游信号分子磷脂酶C-γ - 1偶联，在维持T细胞稳态、调节早期和晚期T细胞发育和分化中起着至关重要的作用。将小鼠体内的内源性LAT替换为Tyr136突变为Phe的形式，导致早期T细胞发育的部分阻滞。然而，随着时间的推移，小鼠患上了一种致命的淋巴增生性疾病，其特征是一种特定的th2型细胞过多。这种矛盾表型的一个后果是自身免疫反应。分析表明，尽管单个LAT残基可能在早期T细胞发育过程中具有积极作用，但它可能在随后的T细胞选择和Th2效应细胞分化过程中负调控信号通路。E. Aguado, S. Richelme, S. Nuñez-Cruz, A. Miazek, A.- m。Mura, m.r ichelme, x.j.。郭德明，何洪涛，何洪涛，LAT受体点突变诱导辅助性T - 2型免疫。科学296,2036-2040(2002)。[摘要]C. L. Sommers, C. s .;李志强，冯志强，李志强，李志强，李志强，李志强，李志强，李志强，李志强，李志强，李志强，李志强，李志强，李志强，李志强，李志强，李志强，李志强，李志强，李志强，李志强，李志强。科学29(6)，2040-2043(2002)。【摘要】【全文】
{"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}
Pub Date : 2002-06-11DOI: 10.1126/scisignal.1362002tw210
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]
我们目前对免疫反应所需的复杂细胞相互作用的理解主要来自体外操作或固定组织内事件的快照。现在有三份报告描述了活体组织内免疫细胞反应的实时分析(见von Adrian的观点)。Miller等人利用双光子技术比较T细胞和B细胞在有组织淋巴组织内的迁移，观察到T细胞比B细胞漫游得更远，速度更快。这种探索行为转向集中聚集抗原的包涵。Stoll等人使用改进的单光子共聚焦成像研究naïve T细胞与淋巴结树突状细胞(DC)抗原的相互作用。随着免疫突触的形成和活化T细胞的最终离开，在抗原负载dc的存在下观察到长时间的连接。Bousso等人利用双光子成像技术研究了在重组胸腺器官培养中胸腺细胞与胸腺基质细胞的相互作用。导致胸腺细胞阳性选择的识别事件促进了胸腺细胞的运动，并增加了胸腺细胞与胸腺基质细胞接触的持续时间。u·h·冯·安德里安，六维T细胞激活。科学296,1815-1817(2002)。[全文]M. J. Miller, I. Parker, M. D. Cahalan，完整淋巴结淋巴细胞运动和抗原反应的双光子成像。科学296,1869-1873(2002)。[摘要]S. Stoll, J. Delon, T. M. Brotz, R. N. Germain，淋巴结T -树突状细胞相互作用的动态成像。科学296,1873-1876(2002)。[摘要]P. Bousso, N. R. Bhakta, R. S. Lewis, E. Robey，双光子显微镜观察胸腺细胞-基质细胞相互作用动力学。科学296,1876-1880(2002)。【摘要】【全文】
{"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}
Pub Date : 2002-06-11DOI: 10.1126/scisignal.1362002tw205
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]
中枢神经系统(CNS)的神经元在损伤后的自我修复能力远不如周围神经系统的神经元。原因可能与环境和周围胶质细胞类型的差异有关，也可能与神经元本身有关。Goldberg等人(见McKerracher和Ellezam的观点)从大鼠身上分离出构成中枢神经系统一部分的视网膜神经节细胞，以研究它们再生轴突的能力。从胚胎大鼠中分离的RGCs比从出生后早期大鼠中分离的RGCs具有更强的轴突再生能力。轴突再生能力的减弱与发育时间有关，在发育时间内，RGC轴突通常会达到其目标，并从轴突生长转变为树突发育。生长模式的转换与细胞固有年龄无关，而是由邻近视网膜细胞的信号引起的。黄晓明，黄晓明，黄晓明，黄晓明，黄晓明，黄晓明，黄晓明，黄晓明，黄晓明，黄晓明，黄晓明。科学296,1860-1864(2002)。[摘要]L. McKerracher, B. Ellezam。科学296,1819-1820(2002)。【摘要】【全文】
{"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}
Pub Date : 2002-06-11DOI: 10.1126/scisignal.1362002tw211
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]
{"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}
Pub Date : 2002-05-07DOI: 10.1126/scisignal.1312002tw171
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]
{"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}
Pub Date : 2002-05-07DOI: 10.1126/scisignal.1312002tw164
Joel Achenbach
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]
运动蛋白是一种分子马达，在细胞周围运输诸如蛋白质和膜囊泡之类的货物。在像神经元这样的极化细胞中，运动蛋白确保运往轴突或树突的货物得到正确的定向。然而，究竟是什么在正确的方向上“操纵”这些马达，目前还不清楚。Setou等人报道了树突状α-氨基-3-羟基-5-甲基异恶唑-4-proprionate (AMPA)受体的亚基之一GluR2的结合蛋白与酪蛋白重链的载货结合区域结合。这种结合蛋白被称为谷氨酸受体相互作用蛋白(GRIP)，与脑神经元树突轴和胞体中的运动蛋白共定位。从富含树突的脑亚细胞部分中，酪蛋白也与GRIP和GluR2共免疫沉淀。GRIP的运动蛋白结合域的表达使内源性运动蛋白在体突区域脱位，而在轴突中不脱位。一个仅含有GRIP结合位点的激酶显性阴性突变体减少了GRIP和GluR2在突触中的定位。另一种支架蛋白称为c-Jun氨基末端激酶相互作用蛋白-1 (JIP)，已知与激酶轻链结合并受轴突定向。因此，神经元的交通可能是由将不同的马达和货物结合在一起的结合蛋白类别所引导的。塞图先生，博士。Seog, Y. Tanaka, Y. Kanai, Y. Takei, M. Kawagishi, N. Hirokawa，谷氨酸受体相互作用蛋白GRIP直接引导驱动蛋白到树突。自然，417,83-87(2002)。(在线期刊)
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Pub Date : 2002-05-07DOI: 10.1126/scisignal.1312002tw170
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]
一个人一生中患上酒精中毒的几率是由遗传倾向和个人对生活事件(如压力)的反应决定的。促肾上腺皮质激素释放激素(CRH)系统调节对应激的内分泌反应，并介导应激相关行为。为了更好地理解应激性饮酒的分子和细胞机制，Sillaber等人创造了缺乏CRH1受体的敲除小鼠。Crhr1−/−小鼠在基础酒精摄入量和偏好方面与野生型小鼠没有差异。然而，在反复的应激事件后，基因敲除小鼠逐渐增加了酒精摄入量，并在其余生中保持高水平。这种饮酒行为的改变伴随着n -甲基- d -天冬氨酸受体NR2B亚基蛋白水平的提高。I. Sillaber, G. Rammes, S. Zimmermann, B. Mahal, W. Zieglgänsberger, W. Wurst, F. Holsboer, R. Spanagel，缺乏功能性CRH1受体的小鼠应激诱导饮酒的增强和延迟。科学296,931-933(2002)。【摘要】【全文】
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Pub Date : 2002-04-23DOI: 10.1126/scisignal.1292002tw149
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]
一小部分T淋巴细胞表达自然杀伤(NK)细胞的特征标记，并已被证明调节适应性免疫反应。与传统T细胞相比，这些NKT细胞的发育尚不清楚，尽管已知它们是由胸腺内主要组织相容性复合物(如CD1配体)积极选择的。Benlagha等人(参见MacDonald的观点)使用四聚体染色来表征野生型胸腺细胞群体中的NKT细胞前体，并追踪它们从胸腺向外周组织的迁移。这些细胞所显示的NK表型实际上是在这些细胞离开胸腺后发生的。更引人注目的是从细胞因子白介素-4到干扰素-γ的表达进展，这可能反映了这些细胞介导的不同免疫调节机制。K. Benlagha, T. Kyin, A. Beavis, L. Teyton, A. Bendelac, NKT细胞谱系的胸腺前体。科学296,553-555(2002)。【摘要】【全文】h.r. MacDonald, T before NK。科学296,481(2002)。【摘要】【全文】
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