University of Groningen
Sorting out cholesterol metabolism
Wijers, Melinde
DOI:
10.33612/diss.102035320
IMPORTANT NOTE: You are advised to consult the publisher's version (publisher's PDF) if you wish to cite from it. Please check the document version below.
Document Version
Publisher's PDF, also known as Version of record
Publication date: 2019
Link to publication in University of Groningen/UMCG research database
Citation for published version (APA):
Wijers, M. (2019). Sorting out cholesterol metabolism: novel insights into the mechanism of endosomal trafficking of lipoprotein receptors. Rijksuniversiteit Groningen. https://doi.org/10.33612/diss.102035320
Copyright
Other than for strictly personal use, 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), unless the work is under an open content license (like Creative Commons).
Take-down policy
If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim.
Downloaded from the University of Groningen/UMCG research database (Pure): http://www.rug.nl/research/portal. For technical reasons the number of authors shown on this cover page is limited to 10 maximum.
Sorting out cholesterol metabolism
Novel insights into the mechanism of endosomal
trafficking of lipoprotein receptors
The research described in this thesis was conducted at the Department
of Pediatrics, section Molecular Genetics, University Medical Center
Groningen, the Netherlands. This work was financially supported
by the Netherlands Organization for Scientific Research (NWO-ALW
grant no. 817.02.022 to BVDS), EU FP7 project TransCard
(FP7-603091-2), the Jan Kornelis de Cock Stichting, the Graduate School
for Drug Exploration (GUIDE), and the University of Groningen.
The printing of this dissertation was financially supported by:
University of Groningen, Groningen, The Netherlands
University Medical Center Groningen, Groningen, The Netherlands
Groningen University Institute of Drug Exploration (GUIDE)
Cover design: Celine Derks
Book layout: Melinde Wijers
Printed by: Ridderprint BV
ISBN: 978-94-034-2110-0 (printed version)
ISBN: 978-94-034-2109-4 (digital version)
©
Melinde Wijers, 2019
No part of this book may be reproduced, stored in retrieval systems,
or transmitted in any form or by any means without prior permission
of the author, or, where applicable, the publisher holding the
copyright on the published articles.
Sorting out cholesterol
metabolism
Novel insights into the mechanism of endosomal
trafficking of lipoprotein receptors
Proefschrift
ter verkrijging van de graad van doctor aan de
Rijksuniversiteit Groningen
op gezag van de
rector magnificus prof. dr. C. Wijmenga
en volgens besluit van het College voor Promoties.
De openbare verdediging zal plaatsvinden op
woensdag 20 november 2019 om 11.00 uur
door
Marthe Elise Wijers
geboren op 20 november 1989
te Groningen
Promotores
Prof. dr. A.J.A. van de Sluis
Prof. dr. J.A. Kuivenhoven
Beoordelingscommissie
Prof dr. S.C.D. van IJzendoorn
Prof. dr. H.H. Kampinga
Prof. dr. N. Zelcer
Contents
Chapter 1 General introduction... 7
Chapter 2 The life cycle of the low-density lipoprotein receptor: insights from
cellular and in-vivo studies... 25
Chapter 3 News on the molecular regulation and function of hepatic low-density
lipoprotein receptor and LDLR-related protein 1... 39
Chapter 4 The COMMD family regulates plasma LDL levels and attenuates
atherosclerosis through stabilizing the CCC complex in endosomal LDLR trafficking... 55
Chapter 5 The hepatic Wiskott-Aldrich syndrome protein and SCAR homologue
(WASH) complex is required for efficient clearance of plasma LDL and HDL cholesterol... 103 Chapter 6 Perturbed lysosomal architecture and localization in liver-specific
WASH-deficient mice does not affect hepatic cholesterol and bile acid metabolism... 135 Chapter 7 General discussion... 153 Appendices Summary... Nederlandse samenvatting... Acknowledgements... List of publications... Curriculum vitae... 170 173 177 182 184
