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Book
Etude des mécanismes contrôlant la libération du domaine intracellulaire du précurseur du peptide amyloïde humain dans les cellules CHO

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The Amyloid Precursor Protein (APP), which plays a central role in Alzheimer’s disease, is a widely expressed cell-surface protein whose normal biological function is poorly understood. The endoproteolytic cleavages of APP, controlled by alpha-, beta- and gamma- secretase activities, lead to the production of soluble APP and amyloid beta-peptide (Aβ). The γ-cleavage is also thought to be responsible for the release of an intracellular C-terminal fragment, named APP intracellular domain (AICD), that is involved in intracellular signalling. Fe65 is an adaptator protein that was reported to interact with AICD, but the role of Fe65 In the processing of APP and the AICD-dependent signalling remain unclear. The aim of our work was to analyze the mechanisms leading to AICD production.
To that end, we transfected APP-Gal4 fusion proteins in CHO cells and measured AICD release by a Gal4 transactivation assay. We first tested the effect of DAPT, a functional gamma-secretase inhibitor. Our data demonstrated, that APP-Gal4 is expressed and processed by the amyloidogenic and non-amyloidogenic pathways in CHO cells. Eight hours of treatment with DAPT (250nM) significantly reduced Aβ production (more than 90% of inhibition), but had no significant affect on Gal4 transactivation . We further showed that Fe65 expression strongly induced Gal4 transactivation. However, we observed that Fe65-transfected cells produced lower levels of extracellular Aβ1-40. We therefore propose that the cleavages leading to extracellular Aβ production and AICD release are different Le précurseur du petite amyloïde (APP), qui joue un rôle central dans la maladie d’Alzheimer, est une protéine membranaire dont la fonction biologique est, à ce jour, encore très peu connue. Les clivages endoprotéolytique de l’APP par les activités α-, β- et γ- sécrétase conduisent à la production d’APP soluble (APPsα) et de peptide amyloïde Aβ. Le clivage γ est également responsable de la libération d’un fragment C-terminal intracellulaire nommée AICD (APP IntraCellular Domain). Celui-ci semble être impliqué dans la signalisation intracellulaire de l’APP.
Fe65 est une protéine adaptatrice qui interagit avec l’AICD mais son rôle dans le métabolisme de l’APP et dans la voie de signalisation dépendante de l’AICD reste encore à élucider. Le but du travail est d’analyser les mécanismes conduisant à la production d’AICD.
Pour cela nous avons exprimé dans des cellules CHO des protéines de fusion APP Gal4 qui permettent de mesurer la libération d’AICD grâce à un test de transactivation de Gal4.
Nos données ont démontré que l’APP Gal4 était exprimé et métabolisé selon les voies cataboliques non-amyloïdogène est amyloïdogène dans les cellules CHO. Nous avosn testé l’effet de DAPT, un inhibiteur fonctionnel de la γ-sécrétase. Huit heures de traitements au DAPT (250nM) réduisent de manière significative ma production de peptide amyloïde (plus de 90% d’inhibition). Cependant, les effets du DAPT mesurés sur la libération d’AICD sont plus faibles. Nous avons ensuite montré que l’expression de Fe65 induisait l’activité transcriptionnelle contrôlée par l’AICD alors qu’elle diminuait la production de peptide amyloïde Aβ. L’ensemble de nos résultats suggère que les clivages menant à la production de peptide amyloïde Aβ et à la libération d’AICD sont distincts


Book
Assessing Cellular Microstructure in Biological Tissues using In Vivo Diffusion-Weighted Magnetic Resonance
Authors: --- ---
Year: 2019 Publisher: Frontiers Media SA

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This eBook is a collection of articles from a Frontiers Research Topic. Frontiers Research Topics are very popular trademarks of the Frontiers Journals Series: they are collections of at least ten articles, all centered on a particular subject. With their unique mix of varied contributions from Original Research to Review Articles, Frontiers Research Topics unify the most influential researchers, the latest key findings and historical advances in a hot research area! Find out more on how to host your own Frontiers Research Topic or contribute to one as an author by contacting the Frontiers Editorial Office: frontiersin.org/about/contact


Book
Assessing Cellular Microstructure in Biological Tissues using In Vivo Diffusion-Weighted Magnetic Resonance
Authors: --- ---
Year: 2019 Publisher: Frontiers Media SA

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Abstract

This eBook is a collection of articles from a Frontiers Research Topic. Frontiers Research Topics are very popular trademarks of the Frontiers Journals Series: they are collections of at least ten articles, all centered on a particular subject. With their unique mix of varied contributions from Original Research to Review Articles, Frontiers Research Topics unify the most influential researchers, the latest key findings and historical advances in a hot research area! Find out more on how to host your own Frontiers Research Topic or contribute to one as an author by contacting the Frontiers Editorial Office: frontiersin.org/about/contact


Book
Assessing Cellular Microstructure in Biological Tissues using In Vivo Diffusion-Weighted Magnetic Resonance
Authors: --- ---
Year: 2019 Publisher: Frontiers Media SA

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Abstract

This eBook is a collection of articles from a Frontiers Research Topic. Frontiers Research Topics are very popular trademarks of the Frontiers Journals Series: they are collections of at least ten articles, all centered on a particular subject. With their unique mix of varied contributions from Original Research to Review Articles, Frontiers Research Topics unify the most influential researchers, the latest key findings and historical advances in a hot research area! Find out more on how to host your own Frontiers Research Topic or contribute to one as an author by contacting the Frontiers Editorial Office: frontiersin.org/about/contact


Book
Histology : a text and atlas : with correlated cell and molecular biology
Authors: ---
ISBN: 9781496383426 1496383427 1496386248 Year: 2020 Publisher: Philadelphia: Wolters Kluwer,

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"Histology: A Text and Atlas is ideal for medical, dental, health professions, and undergraduate biology and cell biology students. This best-selling combination text and atlas includes a detailed textbook, which emphasizes clinical and functional correlates of histology fully supplemented by vividly informative illustrations and photomicrographs. Separate, superbly illustrated atlas sections follow almost every chapter and feature large-size, full-color digital photomicrographs with labels and accompanied descriptions that highlight structural and functional details of cells, tissues, and organs"--


Book
Reconstituting the cytoskeleton
Authors: ---
ISBN: 0123979242 0123984807 Year: 2014 Publisher: San Diego, California : Academic Press,

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This new volume of Methods in Enzymology continues the legacy of this premier serial with quality chapters authored by leaders in the field. This volume covers cytoskeletal structure, including such topics as rotational movement of formins studied by fluorescence polarization microscopy, in vitro assembly assays for bacterial actin filaments, and modulators of microtubule plus end growth.Continues the legacy of this premier serial with quality chapters authored by leaders in the fieldCovers cytoskeletal structureContains chapters with such topics as rec

Mitochondrial disorders in neurology 2
Authors: ---
ISBN: 9780702038631 0702038636 9780750672887 0750672889 Year: 2002 Publisher: [Place of publication not identified] Butterworth Heinemann

Complex intracellular structures in prokaryotes
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ISBN: 9783540325246 3540325247 3642068936 9786610615230 1280615230 3540325263 Year: 2006 Publisher: Berlin ; New York : Springer,

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Provides historical background and comprehensive reviews of ten topics that cover the spectrum of the complex intracellular structures of prokaryotes: proteasomes, phycobilisomes, chlorosomes, gas vesicles, carboxysomes, magnetosomes, intracytoplasmic membranes, membrane-bound nucleoids, anammoxosomes, and cytoarchitecture of Epulopiscium spp.


Book
The Golgi Apparatus : State of the art 110 years after Camillo Golgi's discovery
Authors: ---
ISBN: 9783211763100 3211763090 9783211763094 9786612036576 1282036572 3211763104 Year: 2008 Publisher: Vienna : Springer Vienna : Imprint: Springer,

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The Golgi apparatus is more than 110 years in the center of interest and scientific debates. This book summarizes the data obtained after development of methods of Golgi complex sub fractionation, molecular biology and microscopy collecting a range of expertise, different points of view and different approaches.


Book
Structures and organelles in pathogenic protists
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ISBN: 3642128629 9786612979750 3642128637 1282979752 Year: 2010 Publisher: Berlin ; Heidelberg : Springer,

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Parasitic protozoa, including some which are agents of human and veterinary diseases, display special cytoplasmic structures and organelles. Metabolic pathways have been discovered in these organelles which open up new possibilities for drug targets. This work presents reviews dealing with cytoskeletal structures such as the mastigont system found in trichomonads, the sub-pellicular microtubules in trypanosomatids and the paraflagellar rod. Further chapters cover structures involved in the synthesis, secretion and uptake of molecules, including the flagellar pocket of trypanosomatids, the reservosome of Trypanosoma and the megasome found in Leishmania, the traffic of vesicles in Entamoeba histolytica, secretory organelles and the secretory events of intestinal parasites during encystation. Reviews on special organelles, such as the kinetoplast-mitochondrion complex, the apicoplast found in Apicomplexa, the glycosomes in Kinetoplastida and the acidocalcisomes found in several protozoa complete the volume.

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