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  • 1
    Publication Date: 2010-03-02
    Description: Endocytosis is a complex process fulfilling many cellular and developmental functions. Understanding how it is regulated and integrated with other cellular processes requires a comprehensive analysis of its molecular constituents and general design principles. Here, we developed a new strategy to phenotypically profile the human genome with respect to transferrin (TF) and epidermal growth factor (EGF) endocytosis by combining RNA interference, automated high-resolution confocal microscopy, quantitative multiparametric image analysis and high-performance computing. We identified several novel components of endocytic trafficking, including genes implicated in human diseases. We found that signalling pathways such as Wnt, integrin/cell adhesion, transforming growth factor (TGF)-beta and Notch regulate the endocytic system, and identified new genes involved in cargo sorting to a subset of signalling endosomes. A systems analysis by Bayesian networks further showed that the number, size, concentration of cargo and intracellular position of endosomes are not determined randomly but are subject to specific regulation, thus uncovering novel properties of the endocytic system.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Collinet, Claudio -- Stoter, Martin -- Bradshaw, Charles R -- Samusik, Nikolay -- Rink, Jochen C -- Kenski, Denise -- Habermann, Bianca -- Buchholz, Frank -- Henschel, Robert -- Mueller, Matthias S -- Nagel, Wolfgang E -- Fava, Eugenio -- Kalaidzidis, Yannis -- Zerial, Marino -- England -- Nature. 2010 Mar 11;464(7286):243-9. doi: 10.1038/nature08779. Epub 2010 Feb 28.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Max Planck Institute for Molecular Cell Biology and Genetics, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20190736" target="_blank"〉PubMed〈/a〉
    Keywords: Computing Methodologies ; Endocytosis/*physiology ; Endosomes/metabolism ; Epidermal Growth Factor/metabolism ; Gene Expression Profiling/*methods ; Genome-Wide Association Study ; Humans ; *Image Processing, Computer-Assisted ; Metabolic Networks and Pathways/physiology ; Microscopy, Confocal ; Phenotype ; Protein Transport/physiology ; RNA Interference ; Signal Transduction/physiology ; Transferrin/metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 2
    Publication Date: 2013-08-03
    Description: The rapid, reductive early divisions of many metazoan embryos are followed by the midblastula transition (MBT), during which the cell cycle elongates and zygotic transcription begins. It has been proposed that the increasing nuclear to cytoplasmic (N/C) ratio is critical for controlling the events of the MBT. We show that four DNA replication factors--Cut5, RecQ4, Treslin, and Drf1--are limiting for replication initiation at increasing N/C ratios in vitro and in vivo in Xenopus laevis. The levels of these factors regulate multiple events of the MBT, including the slowing of the cell cycle, the onset of zygotic transcription, and the developmental activation of the kinase Chk1. This work provides a mechanism for how the N/C ratio controls the MBT and shows that the regulation of replication initiation is fundamental for normal embryogenesis.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3898016/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3898016/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Collart, Clara -- Allen, George E -- Bradshaw, Charles R -- Smith, James C -- Zegerman, Philip -- 092096/Wellcome Trust/United Kingdom -- 10-0908/Worldwide Cancer Research/United Kingdom -- C6946/A14492/Cancer Research UK/United Kingdom -- U117597140/Medical Research Council/United Kingdom -- New York, N.Y. -- Science. 2013 Aug 23;341(6148):893-6. doi: 10.1126/science.1241530. Epub 2013 Aug 1.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Wellcome Trust/Cancer Research UK Gurdon Institute, The Henry Wellcome Building of Cancer and Developmental Biology, University of Cambridge, Cambridge CB2 1QN, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23907533" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Blastula/*embryology/metabolism ; Carrier Proteins/*metabolism ; Cell Cycle Proteins/*metabolism ; Chromosomal Proteins, Non-Histone/*metabolism ; *DNA Replication ; RecQ Helicases/*metabolism ; Xenopus Proteins/*metabolism ; Xenopus laevis/*embryology/genetics/metabolism
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 3
    Publication Date: 2013-08-31
    Description: Eggs and oocytes have a remarkable ability to induce transcription of sperm after normal fertilization and in somatic nuclei after somatic cell nuclear transfer. This ability of eggs and oocytes is essential for normal development. Nuclear actin and actin-binding proteins have been shown to contribute to transcription, although their mode of action is elusive. Here, we find that Xenopus Wave1, previously characterized as a protein involved in actin cytoskeleton organization, is present in the oocyte nucleus and is required for efficient transcriptional reprogramming. Moreover, Wave1 knockdown in embryos results in abnormal development and defective hox gene activation. Nuclear Wave1 binds by its WHD domain to active transcription components, and this binding contributes to the action of RNA polymerase II. We identify Wave1 as a maternal reprogramming factor that also has a necessary role in gene activation in development.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3824084/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3824084/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Miyamoto, Kei -- Teperek, Marta -- Yusa, Kosuke -- Allen, George E -- Bradshaw, Charles R -- Gurdon, J B -- 088333/Wellcome Trust/United Kingdom -- 089613/Wellcome Trust/United Kingdom -- 092096/Wellcome Trust/United Kingdom -- 101050/Wellcome Trust/United Kingdom -- 101050/Z/13/Z/Wellcome Trust/United Kingdom -- G1001690/1/Medical Research Council/United Kingdom -- WT077187/Wellcome Trust/United Kingdom -- WT089613/Wellcome Trust/United Kingdom -- New York, N.Y. -- Science. 2013 Aug 30;341(6149):1002-5. doi: 10.1126/science.1240376.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Wellcome Trust/Cancer Research UK Gurdon Institute, The Henry Wellcome Building of Cancer and Developmental Biology, Cambridge, UK. k.miyamoto@gurdon.cam.ac.uk〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23990560" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Nucleus/metabolism ; Cellular Reprogramming/*genetics ; Female ; *Gene Expression Regulation, Developmental ; Gene Knockdown Techniques ; Genes, Homeobox ; Mice ; Nuclear Proteins/genetics/*physiology ; Oocytes/*growth & development/metabolism ; Protein Structure, Tertiary ; RNA Polymerase II/metabolism ; *Transcription, Genetic ; *Transcriptional Activation ; Wiskott-Aldrich Syndrome Protein Family/genetics/*physiology ; Xenopus Proteins/genetics/*physiology ; Xenopus laevis/*embryology/genetics
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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