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Integrin alpha 11 beta 1 is a receptor for collagen XIII

机译:Integrin alpha11β1是胶原蛋白XIII的受体

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Collagen XIII is a conserved transmembrane collagen mainly expressed in mesenchymal tissues. Previously, we have shown that collagen XIII modulates tissue development and homeostasis. Integrins are a family of receptors that mediate signals from the environment into the cells and vice versa. Integrin alpha 11 beta 1 is a collagen receptor known to recognize the GFOGER (O=hydroxyproline) sequence in collagens. Interestingly, collagen XIII and integrin alpha 11 beta 1 both have a role in the regulation of bone homeostasis. To study whether alpha 11 beta 1 is a receptor for collagen XIII, we utilized C2C12 cells transfected to express alpha 11 beta 1 as their only collagen receptor. The interaction between collagen XIII and integrin alpha 11 beta 1 was also confirmed by surface plasmon resonance and pull-down assays. We discovered that integrin alpha 11 beta 1 mediates cell adhesion to two collagenous motifs, namely GPKGER and GF(S)QGEK, that were shown to act as the recognition sites for the integrin alpha 11-I domain. Furthermore, we studied the in vivo significance of the alpha 11 beta 1-collagen XIII interaction by crossbreeding alpha 11 null mice (Itga11(-/-)) with mice overexpressing Col13a1 (Col13a1(oe)). When we evaluated the bone morphology by microcomputed tomography, Col13a1(oe) mice had a drastic bone overgrowth followed by severe osteoporosis, whereas the double mutant mouse line showed a much milder bone phenotype. To conclude, our data identifies integrin alpha 11 beta 1 as a new collagen XIII receptor and demonstrates that this ligand-receptor pair has a role in the maintenance of bone homeostasis.
机译:XIII型胶原是一种主要在间充质组织中表达的保守跨膜胶原。在此之前,我们已经证明,胶原蛋白XIII调节组织发育和体内平衡。整合素是一个受体家族,介导环境信号进入细胞,反之亦然。整合素α11β1是一种已知的胶原受体,可识别胶原中的GFOGER(O=羟脯氨酸)序列。有趣的是,胶原XIII和整合素α11β1都在调节骨内稳态中发挥作用。为了研究α11β1是否是胶原XIII的受体,我们利用转染的C2C12细胞表达α11β1作为其唯一的胶原受体。胶原XIII和整合素α11β1之间的相互作用也通过表面等离子体共振和下拉分析得到证实。我们发现整合素α11β1介导细胞粘附到两个胶原基序,即GPKGER和GF(S)QGEK,它们被证明是整合素α11-I结构域的识别位点。此外,我们通过将α11缺失小鼠(Itga11(-/-)与过度表达Col13a1(Col13a1(oe))的小鼠杂交,研究了α11β1-胶原XIII相互作用的体内意义。当我们通过微计算机断层扫描评估骨形态时,Col13a1(oe)小鼠出现了剧烈的骨过度生长,随后出现了严重的骨质疏松症,而双突变小鼠系显示了更温和的骨表型。总之,我们的数据确定整合素α11β1是一种新的胶原XIII受体,并证明这种配体-受体对在维持骨内稳态中起作用。

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