Syndecan-1 supports integrin alpha2beta1-mediated adhesion to collagen.
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 alpha2beta1-mediated adhesion to collagen. Cells made devoid of HSPGs either by genetic means or by enzymatic digestions were unable to adhere to collagen via alpha2beta1 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 alpha2beta1 integrin-mediated adhesion. Using overexpression and knock-down experiments we demonstrated that syndecan-1, but not syndecan-2 or -4, enhanced binding of alpha2beta1 to collagen. Moreover, syndecan-1 co-localized with alpha2beta1 integrin and contributed to proper organization of cortical actin. Finally, crosstalk between syndecan-1 and alpha2beta1 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 alpha2beta1 and syndecan-1 is important in regulating cell adhesion to collagen and in triggering integrin downstream signalling.
Vuoriluoto
Karoliina
K
VTT Medical Biotechnology, FIN-20520 Turku, Finland.
Jokinen
Johanna
J
Kallio
Katja
K
Salmivirta
Markku
M
Heino
Jyrki
J
Ivaska
Johanna
J
D000199:Actins / Q000378:metabolism; D000818:Animals; D016466:CHO Cells; D002448:Cell Adhesion / Q000502:physiology; D002460:Cell Line; D003094:Collagen / Q000378:metabolism*; D006224:Cricetinae; D003412:Cricetulus; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D019812:Heparan Sulfate Proteoglycans / Q000494:pharmacology / Q000502:physiology*; D038982:Integrin alpha2beta1 / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D010455:Peptides / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D053668:Syndecan-1 / Q000378:metabolism*; D014162:Transfection; D015854:Up-Regulation
D000199:Actins; D019812:Heparan Sulfate Proteoglycans; D038982:Integrin alpha2beta1; D010455:Peptides; D053668:Syndecan-1; D003094:Collagen