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  • 1
    Publication Date: 2013-12-07
    Description: The centrosome is essential for cytotoxic T lymphocyte (CTL) function, contacting the plasma membrane and directing cytotoxic granules for secretion at the immunological synapse. Centrosome docking at the plasma membrane also occurs during cilia formation. The primary cilium, formed in nonhematopoietic cells, is essential for vertebrate Hedgehog (Hh) signaling. Lymphocytes do not form primary cilia, but we found and describe here that Hh signaling played an important role in CTL killing. T cell receptor activation, which "prearms" CTLs with cytotoxic granules, also initiated Hh signaling. Hh pathway activation occurred intracellularly and triggered Rac1 synthesis. These events "prearmed" CTLs for action by promoting the actin remodeling required for centrosome polarization and granule release. Thus, Hh signaling plays a role in CTL function, and the immunological synapse may represent a modified cilium.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4022134/" 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/PMC4022134/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉de la Roche, Maike -- Ritter, Alex T -- Angus, Karen L -- Dinsmore, Colin -- Earnshaw, Charles H -- Reiter, Jeremy F -- Griffiths, Gillian M -- 075880/Wellcome Trust/United Kingdom -- 100140/Wellcome Trust/United Kingdom -- R01 AR054396/AR/NIAMS NIH HHS/ -- R01 GM095941/GM/NIGMS NIH HHS/ -- R01AR05439/AR/NIAMS NIH HHS/ -- R01GM095941/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2013 Dec 6;342(6163):1247-50. doi: 10.1126/science.1244689.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cambridge Institute for Medical Research, University of Cambridge, Hills Road, Cambridge CB2 0XY, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24311692" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; CD8-Positive T-Lymphocytes/*immunology/metabolism ; Cell Polarity ; Cells, Cultured ; Centrosome/metabolism ; *Cytotoxicity, Immunologic ; Hedgehog Proteins/*metabolism ; *Immunological Synapses ; Kruppel-Like Transcription Factors/genetics/metabolism ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Mice, Transgenic ; Models, Immunological ; Neuropeptides/genetics/metabolism ; Receptors, Antigen, T-Cell/immunology/metabolism ; Receptors, Cell Surface/metabolism ; Receptors, G-Protein-Coupled/metabolism ; *Signal Transduction ; T-Lymphocytes, Cytotoxic/*immunology/metabolism ; rac1 GTP-Binding Protein/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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  • 2
    Publication Date: 2014-10-25
    Description: Although fluorescence microscopy provides a crucial window into the physiology of living specimens, many biological processes are too fragile, are too small, or occur too rapidly to see clearly with existing tools. We crafted ultrathin light sheets from two-dimensional optical lattices that allowed us to image three-dimensional (3D) dynamics for hundreds of volumes, often at subsecond intervals, at the diffraction limit and beyond. We applied this to systems spanning four orders of magnitude in space and time, including the diffusion of single transcription factor molecules in stem cell spheroids, the dynamic instability of mitotic microtubules, the immunological synapse, neutrophil motility in a 3D matrix, and embryogenesis in Caenorhabditis elegans and Drosophila melanogaster. The results provide a visceral reminder of the beauty and the complexity of living systems.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4336192/" 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/PMC4336192/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chen, Bi-Chang -- Legant, Wesley R -- Wang, Kai -- Shao, Lin -- Milkie, Daniel E -- Davidson, Michael W -- Janetopoulos, Chris -- Wu, Xufeng S -- Hammer, John A 3rd -- Liu, Zhe -- English, Brian P -- Mimori-Kiyosue, Yuko -- Romero, Daniel P -- Ritter, Alex T -- Lippincott-Schwartz, Jennifer -- Fritz-Laylin, Lillian -- Mullins, R Dyche -- Mitchell, Diana M -- Bembenek, Joshua N -- Reymann, Anne-Cecile -- Bohme, Ralph -- Grill, Stephan W -- Wang, Jennifer T -- Seydoux, Geraldine -- Tulu, U Serdar -- Kiehart, Daniel P -- Betzig, Eric -- GM33830/GM/NIGMS NIH HHS/ -- R01 GM033830/GM/NIGMS NIH HHS/ -- R01GM080370/GM/NIGMS NIH HHS/ -- R01HD37047/HD/NICHD NIH HHS/ -- RM01-GM61010/GM/NIGMS NIH HHS/ -- T32 GM007445/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- Intramural NIH HHS/ -- New York, N.Y. -- Science. 2014 Oct 24;346(6208):1257998. doi: 10.1126/science.1257998. Epub 2014 Oct 23.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA 20147, USA. ; Coleman Technologies, Incorporated, Newtown Square, PA 19073, USA. ; National High Magnetic Field Laboratory and Department of Biological Science, Florida State University, Tallahassee, FL 32310, USA. ; Department of Biological Sciences, University of the Sciences, Philadelphia, PA 19104, USA. ; Laboratory of Cell Biology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA. ; Optical Image Analysis Unit, RIKEN Center for Developmental Biology, Kobe 650-0047, Japan. ; Department of Pharmacology, University of Minnesota, Minneapolis, MN 55455, USA. ; Cell Biology and Metabolism Program, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA. Cambridge Institute for Medical Research, Addenbrooke's Hospital, Cambridge CB2 0XY, England, UK. ; Cell Biology and Metabolism Program, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA. ; Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA. ; Department of Biochemistry and Cellular and Molecular Biology, University of Tennessee, Knoxville, TN 37996, USA. ; Max Planck Institute for Molecular Cell Biology and Genetics, 01307 Dresden, Germany. Max Planck Institute for the Physics of Complex Systems, 01307 Dresden, Germany. ; Department of Molecular Biology and Genetics, Howard Hughes Medical Institute, Center for Cell Dynamics, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA. ; Department of Biology, Duke University, Durham, NC 27708, USA. ; Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA 20147, USA. betzige@janelia.hhmi.org.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25342811" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Caenorhabditis elegans/*embryology ; Cell Communication ; Drosophila melanogaster/*embryology ; Embryo, Nonmammalian/*ultrastructure ; Embryonic Stem Cells/ultrastructure ; Imaging, Three-Dimensional/*methods ; Mice ; Microscopy/*methods ; Molecular Imaging/*methods ; Spheroids, Cellular/ultrastructure
    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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