Vuoriluoto Karoliina, Jokinen Johanna, Kallio Katja, Salmivirta Markku, Heino Jyrki, Ivaska Johanna
VTT Medical Biotechnology, FIN-20520 Turku, Finland.
Exp Cell Res. 2008 Nov 1;314(18):3369-81. doi: 10.1016/j.yexcr.2008.07.005. Epub 2008 Jul 15.
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.
几种不同的受体分子协同作用来调节细胞黏附。其中包括细胞表面蛋白聚糖和整合素，它们在介导细胞与细胞外基质分子纤连蛋白和玻连蛋白的结合中广泛协作。然而，尽管胶原蛋白是人体中最丰富的蛋白质，但对于蛋白聚糖和整合素在细胞与胶原蛋白黏附过程中可能存在的功能协同作用却知之甚少。在此我们表明，细胞表面硫酸乙酰肝素蛋白聚糖（HSPG）支持整合素α2β1介导的与胶原蛋白的黏附。通过基因手段或酶消化使细胞缺乏HSPG后，它们无法通过α2β1整合素黏附于胶原蛋白。缺乏HSPG的细胞在胶原蛋白上的铺展和肌动蛋白组织也受损。在不同的HSPG分子中，发现syndecan-1在支持α2β1整合素介导的黏附中起重要作用。通过过表达和敲低实验，我们证明syndecan-1而非syndecan-2或-4增强了α2β1与胶原蛋白的结合。此外，syndecan-1与α2β1整合素共定位，并有助于皮质肌动蛋白的正确组织。最后，发现syndecan-1与α2β1整合素之间的相互作用可增强基质金属蛋白酶-1在响应胶原蛋白结合时的转录。因此，我们的研究结果表明，整合素α2β1与syndecan-1之间以前未知的联系在调节细胞与胶原蛋白的黏附以及触发整合素下游信号传导中很重要。
