Laminin 5/laminin 332 (LN332) is an adhesion substrate for epithelial cells. After secretion of LN332, a regulated cleavage occurs at the carboxy-terminus of its alpha3 subunit, which releases a tandem of two globular modules named LG4/5. We show that the presence of the LG4/5 domain in precursor LN332 decreases its integrin-mediated cell adhesion properties in comparison with mature LN332. Whereas cell adhesion to the recombinant LG4/5 fragment relies solely on the heparan sulfate proteoglycan (HSPG) receptor syndecan-1, we reveal that both syndecan-1 and the alpha3beta1 integrin bind to precursor LN332. We further demonstrate that syndecan-1 mediated cell adhesion to the LG4/5 fragment and pre-LN332 allows the formation of fascin-containing protrusions, depending on the GTPases Rac and Cdc42 activation. Reducing syndecan-1 expression in normal keratinocytes prevents cell protrusions on pre-LN332 with subsequent failure of the peripheral localization of the alpha3beta1 integrin. We finally show that cell migration on pre-LN332 requires syndecan-1. Therefore, the LG4/5 domain in precursor LN332 appears to trigger intracellular signaling events, which participate in keratinocyte motility.

译文

层粘连蛋白5/层粘连蛋白332 (LN332) 是上皮细胞的粘附底物。LN332分泌后,在其 α3亚基的羧基末端发生受调节的裂解,该裂解释放出两个名为LG4/5的球状模块的串联。我们表明,与成熟的LN332相比,前体LN332中LG4/5结构域的存在降低了其整联蛋白介导的细胞粘附特性。尽管细胞对重组LG4/5片段的粘附仅依赖于硫酸乙酰肝素蛋白聚糖 (HSPG) 受体syndecan-1,但我们揭示了syndecan-1和 α3beta1整联蛋白均与前体ln332结合。我们进一步证明,syndecan-1介导的细胞粘附到LG4/5片段和pre-LN332允许形成含fascin的突起,这取决于GTPases Rac和Cdc42的激活。降低正常角质形成细胞中的syndecan-1表达可防止pre-LN332上的细胞突起,随后 α3β1整联蛋白的外周定位失败。我们最后证明pre-LN332上的细胞迁移需要syndecan-1。因此,前体LN332中的LG4/5结构域似乎触发细胞内信号传导事件,参与角质形成细胞的运动。

+1
+2
100研值 100研值 ¥99课程
检索文献一次
下载文献一次

去下载>

成功解锁2个技能,为你点赞

《SCI写作十大必备语法》
解决你的SCI语法难题!

技能熟练度+1

视频课《玩转文献检索》
让你成为检索达人!

恭喜完成新手挑战

手机微信扫一扫,添加好友领取

免费领《Endnote文献管理工具+教程》

微信扫码, 免费领取

手机登录

获取验证码
登录