SYNTHETIC PEPTIDES THAT MIMIC THE ADHESIVE RECOGNITION SIGNAL OF FIBRONECTIN - DIFFERENTIAL-EFFECTS ON CELL-CELL AND CELL-SUBSTRATUM ADHESION IN EMBRYONIC CHICK-CELLS
SYNTHETIC PEPTIDES THAT MIMIC THE ADHESIVE RECOGNITION SIGNAL OF FIBRONECTIN - DIFFERENTIAL-EFFECTS ON CELL-CELL AND CELL-SUBSTRATUM ADHESION IN EMBRYONIC CHICK-CELLS
复制标题
DOI：
10.1016/0012-1606(87)90399-x
复制
发表时间：
1987-10-01
影响因子：
2.7
通讯作者：
YAMADA, KM
中科院分区：
文献类型：
--
作者：
LASH, JW;LINASK, KK;YAMADA, KM
虽然纤连蛋白已经涉及细胞-细胞以及细胞-基质相互作用，但大多数实验都集中在成纤维细胞的细胞-基质相互作用上。我们已经研究了特定的肽GRGDS来自纤维连接蛋白的细胞结合序列后，使用胚胎细胞和组织的细胞-细胞和细胞-基质相互作用的效果。鸡胚节段板细胞在体节发生的早期阶段经历致密化（即细胞-细胞粘附增加）。纤连蛋白与细胞间相互作用的增加有关。相比之下，心前中胚层经历定向迁移后，纤维连接蛋白丰富的基质，表现出细胞-细胞和细胞-基质的相互作用。分节板细胞是胚胎体节的前体细胞，在培养中通常很少显示细胞与细胞或细胞与基质的相互作用。这些细胞在较低浓度的纤连蛋白衍生肽GRGDS存在下，细胞间粘附显著增加，但没有细胞-基质粘附。在培养物中通常表现出细胞-细胞和细胞-基质粘附的体节细胞，在该肽存在下表现出细胞-基质粘附的完全抑制。在培养物中通常表现出细胞-细胞和细胞-基质粘附的心前中胚层在GRGDS存在下显示出对这两个过程的显著抑制。由于发现一个单价的竞争性抑制剂的纤连蛋白结合可以刺激细胞-细胞粘附是出乎意料的，我们提出了一个“触发”的假设，即肽识别信号作为一个特定的信号或触发器的形态发生过程的压实。这种效应具有显著的特异性，因为即使氨基酸序列发生保守变化的合成肽也没有影响。最后，我们发现在某些条件下，特定肽的作用在6-8小时内丧失，细胞恢复细胞-基质相互作用，或者在节段板细胞的情况下，从压实状态恢复，并表现出细胞-细胞粘附的显著降低。我们的研究表明，细胞和组织的反应可能的多样性，即使是一个单一的肽抑制剂的粘附，我们已经确定了第一个已知的激活作用的纤连蛋白肽对细胞的行为和分化。
Although fibronectin has been implicated in cell-cell as well as cell-substratum interactions, most experimentation has focused on cell-substratum interactions of fibroblasts. We have examined the effect of the specific peptide GRGDS derived from the cell-binding sequence of fibronectin upon cell-cell and cell-substratum interactions using embryonic cells and tissues. Embryonic chick segmental plate cells undergo compaction (i.e. increased cell-cell adhesion) during the early stages of somitogenesis. Fibronectin has been implicated in this increase in cell-cell interaction. In contrast, precardiac mesoderm undergoes directional migration upon a fibronectin-rich substratum, exhibiting both cell-cell and cell-substratum interactions. The segmental plate cell which are the precursors of embryonic somites, normally show very little cell-cell or cell-substratum interaction in culture. These cell exhibit a striking increase in intercellular adhesion, but exhibit no cell-substratum adhesion, in the presence of relatively low concentration of the fibronectin-derived peptide GRGDS. Somite cells, which normally exhibit both cell-cell and cell-substratum adhesion in culture, show complete inhibition of cell-substratum adhesion in the presence of this peptide. precardiac mesoderm, which normally exhibits both cell-cell and cell-substratum adhesion in culture, shows a marked inhibition of both processes in the presence of GRGDS. Since the finding that a monovalent competitive inhibitor of fibronectin binding can stimulate cell-cell adhesion was unexpected, we propose a "trigger" hypothesis, whereby the peptide recognition signal acts as a specific signal or trigger for the morphogenetic process of compaction. There is a striking specificity to this effect, since synthetic peptides with even conservative changes in the amino acid sequence have no effect. Finally, we find that under certain conditions the effect of the specific peptide is lost in 6-8 hr and the cells resume cell-substratum interactions or, in the case of the segmental plate cells, revert from the compacted state and exhibit a substantial decrease in cell-cell adhesion. Our studies indicate the diversity of cell and tissue response possible when even a single peptide inhibitor of adhesion, and we have identified the first known activating effect of a fibronectin peptide on cell behavior and differentiation.