Molecular and mechanical functions of the intermediate filament protein GFAP Stassen, O.M.J.A.
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1 UvA-DARE (Digital Academic Repository) Molecular and mechanical functions of the intermediate filament protein GFAP Stassen, O.M.J.A. Link to publication Citation for published version (APA): Stassen, O. M. J. A. (2016). Molecular and mechanical functions of the intermediate filament protein GFAP General rights It is not permitted to download or to forward/distribute the text or part of it without the consent of the author(s) and/or copyright holder(s), other than for strictly personal, individual use, unless the work is under an open content license (like Creative Commons). Disclaimer/Complaints regulations If you believe that digital publication of certain material infringes any of your rights or (privacy) interests, please let the Library know, stating your reasons. In case of a legitimate complaint, the Library will make the material inaccessible and/or remove it from the website. Please Ask the Library: or a letter to: Library of the University of Amsterdam, Secretariat, Singel 425, 1012 WP Amsterdam, The Netherlands. You will be contacted as soon as possible. UvA-DARE is a service provided by the library of the University of Amsterdam ( Download date: 30 Apr 2018
2 Oscar Stassen Molecular and Mechanical Functions of the Intermediate Filament Protein GFAP Molecular and Mechanical Functions of the Intermediate Filament Protein GFAP - Beyond the Wickerwork - Oscar M.J.A. Stassen 2016
3 Molecular and Mechanical Functions of the Intermediate Filament Protein GFAP Oscar M.J.A. Stassen 2016
4 The research for this thesis was carried out at the Netherlands Institute for Neuroscience, an Institute of the Royal Academy of Arts and Sciences (KNAW), Amsterdam, The Netherlands and at FOM institute for Atomic and Molecular Physics (AMOLF), an Institute of the Foundation for Fundamental Research on Matter (FOM). About the cover: The most remarkable characteristic of intermediate filaments is their beautiful structure of ca. 10 nm thick filaments in aligned bundles. One of the intermediate filaments proteins got its name from this structure, as stated in the 1978 paper by Werner Franke: Vimentin: From the Latin word vimentum, used to describe arrays of flexible rods, both ordered ones (e.g., lattices, filigrees, and wicker-work) and nonordered ones (e.g., brushwood). But as is described in this thesis, there s more to intermediate filaments than that structure, we have to look beyond the wicker-work. Cover Design: Heleen Bijkerk Layout: Oscar Stassen The work described in this thesis is part of the research programme of the Foundation for Fundamental Research on Matter (FOM), which is part of the Netherlands Organisation for Scientific Research (NWO). ISBN: Copyright 2016 by O.M.J.A. Stassen. All rights reserved. No part of this book may be reproduced, transmitted in any form or by any means, or stored in a retrieval system, without prior permission of the author.
5 Molecular and Mechanical Functions of the Intermediate Filament Protein GFAP ACADEMISCH PROEFSCHRIFT ter verkrijging van de graad van doctor aan de Universiteit van Amsterdam op gezag van de Rector Magnificus prof. dr. ir. K.I.J. Maex ten overstaan van een door het College voor Promoties ingestelde commissie, in het openbaar te verdedigen in de Agnietenkapel op vrijdag 2 december 2016, te 12:00 uur door Oscar Maximiliaan Josef Anton Stassen geboren te Venlo
6 Promotiecommissie: Promotores: Prof. dr. E.M. Hol Universiteit van Amsterdam UMC Utrecht Prof. dr. G.H. Koenderink AMOLF VU Amsterdam Copromotor: Dr. W. Kamphuis NIN-KNAW Overige leden: Prof. dr. J.M. Ivaska Prof. dr. J. van Rheenen Prof. dr. M.P. Smidt Prof. dr. W.J. Wadman Prof. dr. C.M. Sahlgren University of Turku, Finland Hubrecht Instituut UMC Utrecht Universiteit van Amsterdam Universiteit van Amsterdam TU Eindhoven University of Turku, Finland Faculteit der Natuurwetenschappen, Wiskunde en Informatica
7 Ὁ βίος βραχύς, ἡ δὲ τέχνη μακρή, ὁ δὲ καιρὸς ὀξύς, ἡ δὲ πεῖρα σφαλερή, ἡ δὲ κρίσις χαλεπή.
8 Table of contents Scope and Outline 7 Chapter 1 - Glial Fibrillary Acidic Protein and Vimentin - cytoskeletal proteins at the crossroads of astrocyte cellular mechanics and signalling Chapter 2 - Mechanical injury is not sufficient to induce a reactive transcriptional program in human astrocytoma cells and human primary astrocytes Chapter 3 - GFAP isoforms control intermediate filament network dynamics, cell morphology and focal adhesions Chapter 4 - GFAPδ/GFAPα ratio correlates with astrocytoma grade and directs astrocytoma gene expression towards a more malignant profile Chapter 5 - IF deficient glia display distinct molecular profiles linked to ECM and cell-cell interactions Chapter 6 - Towards microrheological probing of the effect of GFAP on cell stiffness Chapter 7 - Summary and Discussion 175 References 189 Nederlandse Samenvatting 222 Dankwoord 226 List of Publications 231 Curriculum Vitae 232
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