uu.seUppsala University Publications
Change search
ReferencesLink to record
Permanent link

Direct link
Role of glycosaminoglycans on syndecan-1 in fibroblast growth factor signaling
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
(English)Manuscript (preprint) (Other academic)
National Category
Cell and Molecular Biology
URN: urn:nbn:se:uu:diva-197673OAI: oai:DiVA.org:uu-197673DiVA: diva2:613751
Available from: 2013-04-02 Created: 2013-04-02 Last updated: 2013-08-30
In thesis
1. Syndecan - Regulation and Function of its Glycosaminoglycan Chains
Open this publication in new window or tab >>Syndecan - Regulation and Function of its Glycosaminoglycan Chains
2013 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The cell surface is an active area where extracellular molecules meet their receptors and affect the cellular fate by inducing for example cell proliferation and adhesion. Syndecans and integrins are two transmembrane molecules that have been suggested to fine-tune these activities, possibly in cooperation. Syndecans are proteoglycans, i.e. proteins with specific types of carbohydrate chains attached. These chains are glycosaminoglycans and either heparan sulfate (HS) or chondroitin sulfate (CS). Syndecans are known to influence cell adhesion and signaling. Integrins in turn, are important adhesion molecules that connect the extracellular matrix with the cytoskeleton, and hence can regulate cell motility. In an attempt to study how the two types of glycosaminoglycans attached to syndecan-1 can interact with integrins, a cell based model system was used and functional motility assays were performed. The results showed that HS, but not CS, on the cell surface was capable of regulating integrin-mediated cell motility.

Regulation of intracellular signaling is crucial to prevent abnormal cellular behavior. In the second part of this thesis, the aim was to see how the presentation of glycosaminoglycan chains to the FGF signaling complex could affect the cellular response. When attached to the plasma membrane via syndecan-1, CS chains could support the intracellular signaling, although not promoting as strong signals as HS. When glycosaminoglycans were attached to free ectodomains of syndecan-1, both types of chains sequestered FGF2 from the receptors to the same extent, pointing towards functional overlap between CS and HS.

To further study the interplay between HS and CS, their roles in the formation of pharyngeal cartilage in zebrafish were established. HS was important during chondrocyte intercalation and CS in the formation of the surrounding extracellular matrix. Further, the balance between the biosynthetic enzymes determined the ratio of HS and CS, and HS biosynthesis was prioritized over CS biosynthesis.

The results presented in this thesis provide further insight into the regulation of HS biosynthesis, as well as the roles of both HS and CS on the cell surface. It is evident, that in certain situations there is a strict requirement for a certain HS structure, albeit in other situations there is a functional overlap between HS and CS.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2013. 54 p.
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 884
heparan sulfate, chondroitin sulfate, integrin, cell motility, fibroblast growth factor signaling, pharyngeal cartilage, biosynthesis regulation
National Category
Cell and Molecular Biology
Research subject
Medical Science
urn:nbn:se:uu:diva-197691 (URN)978-91-554-8637-2 (ISBN)
Public defence
2013-05-17, A1:107a, BMC, Husargatan 3, Uppsala, 13:15 (English)
Available from: 2013-04-25 Created: 2013-04-02 Last updated: 2013-08-30Bibliographically approved

Open Access in DiVA

No full text

By organisation
Department of Medical Biochemistry and Microbiology
Cell and Molecular Biology

Search outside of DiVA

GoogleGoogle Scholar
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Total: 206 hits
ReferencesLink to record
Permanent link

Direct link