Journal
EXPERIMENTAL CELL RESEARCH
Volume 314, Issue 18, Pages 3369-3381Publisher
ELSEVIER INC
DOI: 10.1016/j.yexcr.2008.07.005
Keywords
Cell adhesion; Integrin; Syndecan; Collagen
Categories
Funding
- Academy of Finland
- Sigrid Juselius Foundation
- Emil Aaltonen Foundation
- Finnish Cancer Organisations
- EMBO Young Investigator Program
- Finnish Society of University of Turku
- Paulo Foundation
- Finnish Cultural Foundation
- Varsinais-Suomi Regional Fund
- Konkordia association,
- Ida Montini Foundation
- Turku Graduate School for Biomedical Sciences
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Several different receptor molecules act in concert to regulate cell adhesion. Among these are cell-surface proteoglycans and integrins, which collaborate extensively in mediating binding of cells to extracellular matrix molecules fibronectin and vitronectin. However, very little is known about possible functional synergism between proteoglycans and integrins during adhesion of cells to Collagen, although Collagen is the most abundant protein in the human body. Here we show that cell-surface heparan sulphate proteoglycans (HSPGs) support integrin alpha 2 beta 1-mediated adhesion to Collagen. Cells made devoid of HSPGs either by genetic means or by enzymatic digestions were unable to adhere to collagen via alpha 2 beta 1 integrin. HSPG-deficient cells also displayed impaired spreading and actin organization on Collagen. Among different HSPG molecules syndecan-1 was found to play an important role in supporting alpha 2 beta 1 integrin-mediated adhesion. Using overexpression and knock-clown experiments we demonstrated that syndecan-1, but not syndecan-2 or -4, enhanced binding of alpha 2 beta 1 to collagen. Moreover, syndecan-1 co-localized with alpha 2 beta 1 integrin and contributed to proper organization of cortical actin. Finally, crosstalk between syndecan-1 and alpha 2 beta 1 integrin was found to enhance the transcription of matrix metalloproteinase-1 in response to Collagen binding. Our findings thus suggest that a previously unknown link between integrin alpha 2 beta 1 and synclecan-1 is important in regulating cell adhesion to Collagen and in triggering integrin downstream signalling. (c) 2008 Elsevier Inc. All rights reserved.
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