University of Oulu

Golgi pH and glycosylation

Saved in:
Author: Rivinoja, Antti1
Organizations: 1University of Oulu, Faculty of Science, Department of Biochemistry
Format: ebook
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 2.8 MB)
Persistent link:
Language: English
Published: 2009
Publish Date: 2009-10-13
Thesis type: Doctoral Dissertation
Defence Note: Academic dissertation to be presented with the assent of the Faculty of Science of the University of Oulu for public defence in Auditorium IT115, Linnanmaa, on 23 October 2009, at 12 noon
Reviewer: Docent Esa Kuismanen
Docent Vesa Olkkonen


Glycans, as a part of glycoproteins, glycolipids and other glycoconjugates, are involved in many vital intra- and inter-cellular tasks, such as protein folding and sorting, protein quality control, vesicular trafficking, cell signalling, immunological defence, cell motility and adhesion. Therefore, their correct construction is crucial for the normal functioning of eukaryotic cells and organisms they form. Most cellular glycans are constructed in the Golgi, and abnormalities in their structure may derive, for instance, from alkalinization of the Golgi lumen.

In this work we show that Golgi pH is generally higher and more variable in abnormally glycosylating, i.e. strongly T-antigen (Gal-β1,3-GalNAc-ser/thr) expressing cancer cells, than in non-T-antigen expressing cells. We also confirmed that the Golgi pH alterations detected in cancer cells have the potential to induce glycosylation changes. A mere 0.2 pH unit increase in Golgi pH is able to induce T-antigen expression and inhibit terminal N-glycosylation in normally glycosylating cells. The mechanism of inhibition involves mislocalization of the corresponding glycosyltransferases.

We also studied potential factors that can promote Golgi pH misregulation in health and disease, and found that cultured cancer cells, despite variation and elevation in Golgi pH, are fully capable of acidifying the Golgi lumen under the normal Golgi pH. Moreover, we introduce a Golgi localized Cl-/HCO3- exchanger, AE2a, that participates in Golgi pH regulation by altering luminal bicarbonate concentration and thus also buffering capacity. Participation of AE2a in Golgi pH regulation is especially intriguing, because it also provides a novel mechanism for expelling protons from the Golgi lumen.

see all

Series: Acta Universitatis Ouluensis. A, Scientiae rerum naturalium
ISSN-E: 1796-220X
ISBN: 978-951-42-9269-9
ISBN Print: 978-951-42-9268-2
Issue: 535
Copyright information: © University of Oulu, 2009. This publication is copyrighted. You may download, display and print it for your own personal use. Commercial use is prohibited.