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The Mutual Impact of Syndecan-1 and Its Glycosaminoglycan Chains-A Multivariable Puzzle
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.
2012 (English)In: Journal of Histochemistry and Cytochemistry, ISSN 0022-1554, E-ISSN 1551-5044, Vol. 60, no 12, 936-942 p.Article in journal (Refereed) Published
Abstract [en]

Proteoglycans, with their core proteins and attached glycosaminoglycan chains, are recognized as important partners in many biological processes, yet often experimental analysis of their molecular action is considered for only part of these molecules: either the protein or the carbohydrate unit. In this article, we have tried to summarize, with an example of the syndecan family in general and more specifically with syndecan-1, what is known considering the mutual influence of these different components, and we follow whether the nature of the glycosaminoglycan chains matters for these effects. 

Place, publisher, year, edition, pages
2012. Vol. 60, no 12, 936-942 p.
Keyword [en]
syndecan-1, proteoglycan, glycosaminoglycan, heparan sulfate, chondroitin sulfate, function, interaction
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-190326DOI: 10.1369/0022155412460242ISI: 000311683500006OAI: oai:DiVA.org:uu-190326DiVA: diva2:585870
Available from: 2013-01-10 Created: 2013-01-07 Last updated: 2013-08-30Bibliographically approved
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

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Eriksson, Anna S.Spillmann, Dorothe
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