Science's STKEPub Date : 2003-04-29DOI: 10.1126/scisignal.1802003tw165
{"title":"PPARδ: Burning off the Fat","authors":"","doi":"10.1126/scisignal.1802003tw165","DOIUrl":"https://doi.org/10.1126/scisignal.1802003tw165","url":null,"abstract":"Energy consumption and fat metabolism are the keys to controlling weight gain. Peroxisome proliferator-activated receptors (PPARs) are essential regulators of lipid storage and metabolism. The three isoforms of PPARs--PPARα, PPARγ, PPARδ--exhibit tissue-specific expression and functions. PPARγ stimulates adipogenesis and lipid storage, whereas PPARα stimulates lipid combustion in the liver. The role of PPARδ had not been determined. Wang et al. used transgenic mice overexpressing PPARδ in adipose tissue to show that PPARδ inhibited weight gain and blocked fat storage. In adipose tissue from the transgenic mice, PPARδ promoted expression of β oxidation enzymes, triglyceride hydrolysis enzymes involved in lipid metabolism, and of proteins that uncouple mitochondria, which allows cellular energy stores to be converted to heat (thermogenesis). In cultured cells overexpressing PPARδ, β-oxidation and triglyceride metabolism were increased in response to a PPARδ agonist. The effects of PPARδ were very similar to those of the transcriptional coactivator PGC-1α (peroxisome proliferator-activated receptor gamma coactivator-1α) and in cultured cells or gastrocnemius muscle. PPARδ and PGC-1α coprecipitated, which suggested that the thermogenic effects of PGC-1α may be mediated through interaction with PPARδ. PPARδ agonists may provide yet another target in the war against obesity. Y.-X. Wang, C.-H. Lee, S. Tiep, R. T. Yu, J. Ham, H. Kang, R. M. Evans, Peroxisome-proliferator-activated receptor δ activates fat metabolism to prevent obesity. Cell 113, 159-170 (2003). [Online Journal]","PeriodicalId":21619,"journal":{"name":"Science's STKE","volume":"70 1","pages":"TW165 - tw165"},"PeriodicalIF":0.0,"publicationDate":"2003-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80591898","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 : 2003-04-01DOI: 10.1126/scisignal.1762003tw127
{"title":"Dissecting Growth Cone Guidance","authors":"","doi":"10.1126/scisignal.1762003tw127","DOIUrl":"https://doi.org/10.1126/scisignal.1762003tw127","url":null,"abstract":"The growth cones of developing neurons take s and turns that allow them to reach the appropriate target. Their path is guided by responses to attractive and repulsive cues from chemotropic ligands that they encounter along the way. These ligands activate receptors on the surface of the growth cone. Campbell and Holt describe new insights into the signaling pathways that are integrated to process such guidance cues. They report that in cultured Xenopus retinal growth cones, three different chemotropic ligands, netrin-1, semaphorin3A (Sema3A), and lysophosphatidic acid (LPA) stimulate distinct, but overlapping, signaling pathways. Netrin-1 and Sema3A activated the p42 and p44 mitogen-activated protein kinases (MAPKs). The p38 MAPK, normally associated with stress responses, was activated in cells treated with netrin-1 or LPA. Experiments with pharmacological inhibitors of the kinases indicated that the MAPK responses were necessary for axon guidance. Studies with antibodies to the active, cleaved form of caspase-3 revealed that caspase-3 was activated in response to LPA or netrin-1, and again, inhibitors were used to show that caspase activity was required for chemotropic responses in vitro. The authors discuss the potential role of caspase-3--better known as a component of pathways leading to apoptosis or cell death--in axon guidance. The authors further note similarities between the chemotropic pathways implicated in the present work with those thought to regulate synaptic plasticity. C. S. Campbell, C. E. Holt, Apoptotic pathway and MAPKs differentially regulate chemotropic responses of retinal growth cones. Neuron 37, 939-952 (2003). [Online Journal]","PeriodicalId":21619,"journal":{"name":"Science's STKE","volume":"83 1","pages":"TW127 - tw127"},"PeriodicalIF":0.0,"publicationDate":"2003-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74847931","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 : 2003-02-25DOI: 10.1126/scisignal.1712003tw83
{"title":"Translating Memories","authors":"","doi":"10.1126/scisignal.1712003tw83","DOIUrl":"https://doi.org/10.1126/scisignal.1712003tw83","url":null,"abstract":"Formation of long-term memory clearly requires transcriptional responses in neurons, but the identity of the expressed genes has been difficult to track down. Dubnau et al. used a combined strategy in which they analyzed DNA microarrays for transcripts whose abundance was increased during formation of long-term memories and also screened for Drosophila mutants with impaired long-term memory. Several genes that showed up in both screens encode proteins that take part in transport and localized translation of mRNA, a process already implicated in memory storage mechanisms. One gene, pumilio, works to repress translation of specific transcripts, and another, staufen, encodes a protein that functions in translocation of mRNAs. Studies with temperature-sensitive staufen mutants showed that loss of that gene product during a one-day period after training blocked memory formation, effectively ruling out other nonspecific actions of the staufen mutation. The authors propose that particles containing mRNAs are transported to synapses activated during the learning stimulus. Components like pumilio may repress translation along the way until the complex reaches its appropriate synaptic target. Greenspan provides insightful commentary and amusing historical background. J. Dubnau, A.-S. Chiang, L. Grady, J. Barditch, S. Gossweiler, J. McNeil, P. Smith, F. Buldoc, R. Scott, U. Certa, C. Broger, T. Tully, The staufen/pumilio pathway is involved in Drosophila long-term memory. Curr. Biol. 13, 286-296 (2003). [Online Journal] J. Greenspan, RNA and memory: From feeding to localization. Curr. Biol. 13, R126-R127 (2003). [Online Journal]","PeriodicalId":21619,"journal":{"name":"Science's STKE","volume":"64 1","pages":"TW83 - tw83"},"PeriodicalIF":0.0,"publicationDate":"2003-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80182852","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 : 2003-02-18DOI: 10.1126/scisignal.1702003tw75
{"title":"Flexible Management","authors":"","doi":"10.1126/scisignal.1702003tw75","DOIUrl":"https://doi.org/10.1126/scisignal.1702003tw75","url":null,"abstract":"Scaffolding proteins contain binding sites for individual components of signal pathways and are thought to serve as grand organizing centers. Park et al. (see the Perspective by Ptashne and Gann) explored the basic physical requirements for a scaffold recruitment interaction using the yeast mitogen-activating protein kinase (MAPK) signaling pathways as a model system. Replacing defective scaffold-kinase recruitment interactions with completely different protein-protein interactions restored proper signaling, thus demonstrating the tremendous plasticity of these organizing factors. Such flexibility likely underlies the evolution of new pathways and resembles that of binding sites in transcription factors. S.-H. Park, A. Zarrinpar, W. A. Lim, Rewiring MAP kinase pathways using alternative scaffold assembly mechanisms. Science 299, 1061-1064 (2003). [Abstract] [Full Text] M. Ptashne, A. Gann, Imposing specificity on kinases. Science 299, 1025-1027 (2003). [Summary] [Full Text]","PeriodicalId":21619,"journal":{"name":"Science's STKE","volume":"24 1","pages":"TW75 - tw75"},"PeriodicalIF":0.0,"publicationDate":"2003-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83259742","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 : 2003-02-11DOI: 10.1126/scisignal.1692003tw65
{"title":"Chloroplast Synthesis Under the GUN","authors":"","doi":"10.1126/scisignal.1692003tw65","DOIUrl":"https://doi.org/10.1126/scisignal.1692003tw65","url":null,"abstract":"The chloroplast, the light-converting energy factory of the plant cell, is a complex assemblage of proteins, of which only a portion are actually encoded within the chloroplast genome. The nucleus and the chloroplast thus must carry on a highly coordinated conversation not only to supply the chloroplast with its requisite components, but also to coordinate chloroplast function with other aspects of the cell's development and physiology. Encoded by the nucleus but resident in the plastid, the GUN4 protein is key to chlorophyll synthesis. Larkin et al. now find that GUN4 functions by controlling the synthesis of a signaling intermediate, Mg-protoporphyrin IX, through its actions on the Mg chelatase enzyme. R. M. Larkin, J. M. Alonso, J. R. Ecker, J. Chory, GUN4, a regulator of chlorophyll synthesis and intracellular signaling. Science 299, 902-906 (2003). [Abstract] [Full Text]","PeriodicalId":21619,"journal":{"name":"Science's STKE","volume":"46 1","pages":"TW65 - tw65"},"PeriodicalIF":0.0,"publicationDate":"2003-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86830017","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 : 2003-01-14DOI: 10.1126/scisignal.1652003tw25
{"title":"Faulty Connections Between Circulatory Paths","authors":"","doi":"10.1126/scisignal.1652003tw25","DOIUrl":"https://doi.org/10.1126/scisignal.1652003tw25","url":null,"abstract":"The parallel circulatory systems of blood and lymph separate during development through the differentiation of blood vessel endothelium. Abtahian et al. (see the Perspective by Jain and Padera) now show that this separation depends on specific intracellular signaling proteins--SLP-76 and Syk--known to be required for correct lymphocyte and platelet function. Abnormal connections between blood and lymphatic vessels occurred in mice lacking either protein and led to severe circulatory defects and hemorrhage. Surprisingly, expression of SLP-76 was not detected on endothelial cells, and abnormal connections occurred in wild-type mice that had been irradiated and received SLP-76-deficient bone marrow. These results suggest that cells of a hematopoietic lineage are required to help coordinate separation of the two vascular systems. F. Abtahian, A. Guerriero, E. Sebzda, M.-M. Lu, R. Zhou, A. Mocsai, E. E. Myers, B. Huang, D. G. Jackson, V. A. Ferrari, V. Tybulewicz, C. A. Lowell, J. J. Lepore, G. A. Koretzky, M. L. Kahn, Regulation of blood and lymphatic vascular separation by signaling proteins SLP-76 and Syk. Science 299, 247-251 (2003). [Abstract] [Full Text] R. K. Jain, T. P. Padera, Lymphatics make the break. Science 299, 209-210 (2003). [Summary] [Full Text]","PeriodicalId":21619,"journal":{"name":"Science's STKE","volume":"110 1","pages":"TW25 - tw25"},"PeriodicalIF":0.0,"publicationDate":"2003-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87707590","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 : 2003-01-07DOI: 10.1126/scisignal.1642003tw13
{"title":"Gas-Driven Transcriptional Regulation","authors":"","doi":"10.1126/scisignal.1642003tw13","DOIUrl":"https://doi.org/10.1126/scisignal.1642003tw13","url":null,"abstract":"Gene expression in mammalian cells is controlled by environmental and metabolic cues, but little is known about the molecular mechanisms that sense and respond to these cues. Dioum et al. (see the Perspective by Boehning and Snyder) have discovered one intriguing mechanism in a study of NPAS2 (neuronal PAS domain protein 2), a transcription factor implicated in the control of circadian rhythms. NPAS2 was shown to bind heme as a prosthetic group, and the heme, in turn, was shown to function as a gas-regulated sensor. In experiments with purified proteins, carbon monoxide (CO) was identified as a candidate ligand for this sensor. Exposure to CO inhibited the dimerization of NPAS2 with BMAL1, the protein that confers the transcription factor with DNA binding activity. E. M. Dioum, J. Rutter, J. R. Tuckerman, G. Gonzalez, M.-A. Gilles-Gonzalez, S. L. McKnight, NPAS2: A gas-responsive transcription factor. Science 298, 2385-2387 (2002). [Abstract] [Full Text] D. Boehning, S. H. Snyder, Carbon monoxide and clocks. Science 298, 2339-2340 (2002). [Summary] [Full Text]","PeriodicalId":21619,"journal":{"name":"Science's STKE","volume":"31 1","pages":"TW13 - tw13"},"PeriodicalIF":0.0,"publicationDate":"2003-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78138714","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 : 2003-01-07DOI: 10.1126/scisignal.1642003tw16
{"title":"Mother Nose Best","authors":"","doi":"10.1126/scisignal.1642003tw16","DOIUrl":"https://doi.org/10.1126/scisignal.1642003tw16","url":null,"abstract":"Changes in the numbers of olfactory neurons or in neuroblast migration to the olfactory bulb can affect abilities to discriminate odors or establish new odor-related memories. Studying female mice, Shingo et al. show that the hormone prolactin induces increased production of olfactory cell precursors. The prolactin-induced changes were apparent during pregnancy and also just after mating. Odor discrimination contributes to recognition of mates and offspring. These insights into prolactin-regulated neurogenesis may provide a physiological basis for understanding certain complex, seemingly social, behaviors. T. Shingo, C. Gregg, E. Enwere, H. Fujikawa, R. Hassam, C. Geary, J. C. Cross, S. Weiss, Pregnancy-stimulated neurogenesis in the adult female forebrain mediated by prolactin. Science 299, 117-120 (2003). [Abstract] [Full Text]","PeriodicalId":21619,"journal":{"name":"Science's STKE","volume":"32 1","pages":"TW16 - tw16"},"PeriodicalIF":0.0,"publicationDate":"2003-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83196129","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 : 2002-12-10DOI: 10.1126/scisignal.1622002tw468
{"title":"From General to Specific","authors":"","doi":"10.1126/scisignal.1622002tw468","DOIUrl":"https://doi.org/10.1126/scisignal.1622002tw468","url":null,"abstract":"In vitro studies and work done in yeast have suggested that the transcription factor DRAP1 functions as a \"general\" transcriptional regulator that represses transcription by preventing the interaction of TFIIB with TBP (the TATA box-binding protein of TFIIB). Iratni et al. examined the function of DRAP1during early mouse development and found that the mutant embryo exhibited gastrulation defects consistent with increased activity of Nodal, a secreted morphogen of the transforming growth factor-β family that is the primary inducer of mesoderm during gastrulation. Nodal signaling is inhibited in the early embryo by DRAP1, most likely through its interaction with FoxH1. Thus, a factor that was previously thought to be a general transcriptional regulator displays a specific role in embryonic patterning through the regulation of Nodal's positive feedback loop, providing a mechanism for regulation of morphogen signaling. R. Iratni, Y.-T. Yan, C. Chen, J. Ding, Y. Zhang, S. M. Price, D. Reinberg, M. M. Shen, Inhibition of excess nodal signaling during mouse gastrulation by the transcriptional corepressor DRAP1. Science 298, 1996-1999 (2002). [Abstract] [Full Text]","PeriodicalId":21619,"journal":{"name":"Science's STKE","volume":"35 1","pages":"TW468 - tw468"},"PeriodicalIF":0.0,"publicationDate":"2002-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75974075","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 : 2002-12-03DOI: 10.1126/scisignal.1612002tw454
{"title":"The Whens and Wheres of Neural Expression","authors":"","doi":"10.1126/scisignal.1612002tw454","DOIUrl":"https://doi.org/10.1126/scisignal.1612002tw454","url":null,"abstract":"For normal organ and tissue development and function, certain genes must be expressed at the appropriate place and time. For example, neural genes must be expressed in neural tissue but shut down in nonneural tissues. Lunyak et al. examined mechanisms by which neural-specific gene expression can be restricted from nonneural tissues. The zinc-finger transcription factor REST/NRSF can mediate extraneural restriction through two different mechanisms, one of which uses active repression via a histone deacetylation complex and one that involves gene silencing via DNA methylation and the recruitment of the corepressor CoREST and silencing machinery. The latter mechanism can mediate gene silencing of specific chromosomal regions, including gene clusters encompassing neuron-specific genes, some of which do not themselves contain REST/NRSF response elements. V. V. Lunyak, R. Burgess, G. G. Prefontaine, C. Nelson, S.-H. Sze, J. Chenoweth, P. Schwartz, P. A. Pevzner, C. Glass, G. Mandel, M. G. Rosenfeld, Corepressor-dependent silencing of chromosomal regions encoding neuronal genes. Science 298, 1747-1752 (2002). [Abstract] [Full Text]","PeriodicalId":21619,"journal":{"name":"Science's STKE","volume":"38 1","pages":"tw454 - tw454"},"PeriodicalIF":0.0,"publicationDate":"2002-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87987930","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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