Publications
Download:
File size:
438 kb
Format:
application/pdf
Author:
Håberg, Karin (Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics) (Sven Carlsson)
Title:
Membrane-remodeling by SNX18 in endosomal transport and autophagy
Alternative title (sv) :
SNX18 - ett membranaktivt protein vid endosomal transport och autofagi
Department:
Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics
Publication type:
Doctoral thesis, comprehensive summary (Other academic)
Language:
English
Publisher: Department of Medical Biochemistry and Biophysics, Umeå University
Pages:
42
Series:
Umeå University medical dissertations, ISSN 0346-6612; 1478
Year of publ.:
2012
URI:
urn:nbn:se:umu:diva-51999
Permanent link:
http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-51999
ISBN:
978-91-7459-366-2
Subject category:
Cell and Molecular Biology
Research subject:
Medical Biochemistry
Keywords(en) :
Sorting nexin, SNX9-family, SNX18, endosomal transport, autophagy
Abstract(en) :

The intracellular space of eukaryotic cells is subdivided into functionally distinct membrane-enclosed organelles. Regulation of these intracellular membranes requires an intricate network of specialized lipids and proteins that maintain organellar integrity and mediate transport between organelles. Proteins of the sorting nexin (SNX) family are membrane-binding regulators of transport events within the endomembrane system. The endomembrane system includes organelles associated with endocytic, secretory and degradative processes in the cell. The aims of this thesis were to functionally characterize SNX18 and SNX33, members of the SNX9-subfamily of sorting nexins, and to elucidate the role of SNX18 in autophagy.

We demonstrated that all three proteins in the SNX9-family are capable of both membrane binding and remodeling, and interact with the membrane scission enzyme dynamin. We found that SNX18 localizes to endosomal structures in the endomembrane system, together with several identified factors previously described as regulators of endosomal transport. These results indicate that SNX18 mediates budding of membrane carriers in endosomal trafficking. In addition to this, knockdown of SNX18 in cultured cells was found to inhibit autophagy. Autophagy is a catabolic process by which cells degrade and recycle cellular components. It is a cellular response to various stress conditions such as oxidative stress, nutrient deprivation and infections. The components destined for degradation by autophagy are sequestered into a double-membrane structure called the autophagosome in which they are delivered to the lysosome. SNX18 interacts directly with proteins connected to autophagosome formation. Moreover, we demonstrated that the membrane-remodeling capability of SNX18 is a prerequisite for autophagosome formation.

Taken together, our results lead to the conclusions that SNX18 remodels cellular membranes during formation of carriers for endosomal transport and that it is a positive regulator of autophagy and autophagosome formation.

Public defence:
2012-02-29, KB3A9, KBC-huset, Linnaeus väg, Umeå Universitet, Umeå, 09:00 (English)
Degree:
Doctor of Philosophy (PhD)
Supervisor:
Carlsson, Sven, Professor (Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics)
Opponent:
Bjørkøy, Geir, Professor (Department of Cancer Research and Molecular Medicine, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway)
Available from:
2012-02-08
Created:
2012-02-07
Last updated:
2012-02-08
Statistics:
2161 hits
FILE INFORMATION
File size:
438 kb
Mimetype:
application/pdf
Type:
fulltext
Statistics:
331 hits