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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >PDGF-A interactions with fibronectin reveal a critical role for heparan sulfate in directed cell migration during Xenopus gastrulation
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PDGF-A interactions with fibronectin reveal a critical role for heparan sulfate in directed cell migration during Xenopus gastrulation

机译：PDGF-A与纤连蛋白的相互作用揭示了硫酸乙酰肝素在非洲爪蟾成胃过程中定向细胞迁移中的关键作用

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摘要

Platelet-derived growth factor (PDGF) signaling is essential for processes involving cell motility and differentiation during embryonic development in a wide variety of organisms including the mouse, frog, zebrafish, and sea urchin. In early Xenopus laevis embryos, PDGF-AA provides guidance cues for the migration of anterior mesendoderm cells as they move across a fibronectin-rich extracellular matrix. The long form of PDGF-A includes a positively charged carboxyl-terminal retention motif that can interact with the extracellular matrix and heparan sulfate proteoglycans (HSPGs). In this study we demonstrate that PDGF-AA binds directly to fibronectin and that this association is greatly enhanced by heparin. The PDGF-AA-fibronectin binding occurs across a broad range of pHs (5.5-9), which is significant because the PDGF-guided migration of Xenopus mesendoderm cells occurs under basic extracellular conditions (pH 8.4). We further demonstrate that endogenous HSPG's are required for the PDGF-AA-guided mesendoderm movement, suggesting an in vivo role for HSPGs in mediating the interaction between PDGF-AA and fibronectin.
机译：血小板衍生的生长因子（PDGF）信号对于包括老鼠，青蛙，斑马鱼和海胆在内的多种生物在胚胎发育过程中涉及细胞运动和分化的过程至关重要。在非洲爪蟾早期胚胎中，PDGF-AA为前中胚层细胞在富含纤连蛋白的细胞外基质中移动时的迁移提供了指导。 PDGF-A的长形式包括带正电荷的羧基末端保留基序，可以与细胞外基质和硫酸乙酰肝素蛋白聚糖（HSPG）相互作用。在这项研究中，我们证明了PDGF-AA直接与纤连蛋白结合，并且肝素大大增强了这种联系。 PDGF-AA-纤连蛋白的结合在很宽的pH值范围内（5.5-9）发生，这很重要，因为PDGF指导的爪蟾中胚层细胞的迁移发生在基本的细胞外条件（pH 8.4）下。我们进一步证明，PDGF-AA引导的中胚层运动需要内源性HSPG，这提示HSPG在介导PDGF-AA与纤连蛋白之间的相互作用中具有体内作用。

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  • 作者

    Erin M. Smith; Maria Mitsi; Matthew A. Nugent; Karen Symes;

  • 作者单位

    Department of Biochemistry, Boston University School of Medicine, 72 East Concord Street, Boston, MA 02118;

    Department of Biochemistry, Boston University School of Medicine, 72 East Concord Street, Boston, MA 02118 Institute of Biologically Oriented Materials, Eidgenoessische Technische Hochschule Zuerich, Wolfgang-Pauli-Strasse 10, HCI F443 (Hoenggerberg), CH-8093 Zuerich, Switzerland;

    Department of Biochemistry, Boston University School of Medicine, 72 East Concord Street, Boston, MA 02118;

    Department of Biochemistry, Boston University School of Medicine, 72 East Concord Street, Boston, MA 02118;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
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  • 关键词

    embryo; embryonic development; mesendoderm; mesoderm;

    机译：胚胎胚胎发育;中胚层;中胚层;

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