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alpha3亚基的羧基末端发生有规律的切割,释放出串联的两个球形模块LG4 / 5。我们显示,与成熟的LN332相比,前体LN332中LG4 / 5域的存在降低了其整合素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,但我们发现syndecan-1和alpha3beta1整联蛋白均与前体LN332结合。我们进一步证明了syndecan-1介导的细胞粘附到LG4 / 5片段和pre-LN332允许形成含有fascin的突起,具体取决于GTPa​​ses Rac和Cdc42的激活。减少正常角质形成细胞中syndecan-1的表达可以防止pre-LN332上的细胞突出,并随后导致alpha3beta1整联蛋白的外周定位失败。我们最终证明,前LN332上的细胞迁移需要syndecan-1。因此,前体LN332中的LG4 / 5结构域似乎触发了细胞内信号传导事件,该事件参与了角质形成细胞的运动。

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