Dissociation of the complex between CD151 and laminin-binding integrins permits migration of epithelial cells

Dissociation of the complex between CD151 and laminin-binding integrins permits migration of epithelial cells
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DOI:
10.1016/j.yexcr.2005.12.034
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发表时间:
2006-04-15
影响因子:
3.7
通讯作者:
Aumailley, M
Aumailley, M
中科院分区:
医学3区
文献类型:
--
作者:
Chometon, G;Zhang, ZG;Aumailley, M

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层粘连蛋白结合整合素与CD151形成复合物,CD151是四蛋白家族的一员,被认为参与细胞迁移的调节。在表皮中,CD151分别与α 3 β 1和α 6 β 4整合素定位在细胞-细胞和细胞-基质接触处,这是非迁移细胞的特征结构。利用CD151, TS151r的单克隆抗体,我们研究了CD151在上皮细胞迁移中的作用,TS151r的表位与tetraspanin整合素结合位点重叠。在标准培养条件下,上皮HaCaT细胞在层粘连蛋白上的迁移能力较低,这显然是内源性层粘连蛋白5所致。然而,用TS151r挑战HaCaT细胞允许肌动蛋白细胞骨架的重排,细胞-细胞和β 4整合素介导的细胞-基质接触和细胞迁移的拆除。在体内,毛囊间表皮静息上皮细胞中不存在游离CD151,所有CD151都在细胞间和细胞基质接触中与整合素结合。相比之下,游离CD151存在于生长期毛囊较深区域上皮片的细胞间接触处,被认为含有迁移细胞。总之,这些结果强烈表明,cd151 -整合素复合物的解离允许上皮细胞与细胞外基质的相互作用和细胞迁移的重塑。(c) 2006爱思唯尔公司版权所有。
Laminin-binding integrins form a complex with CD151, a member of the tetraspanin family suggested to be involved in the regulation of cell migration. in the epidermis, CD151 is localized with alpha 3 beta 1 and alpha 6 beta 4 integrins at cell-cell and cell-matrix contacts, respectively, characteristic structures of non-migrating cells. Taking advantage of a monoclonal antibody against CD151, TS151r, which epitope overlaps with the tetraspanin integrin-binding site, we have investigated the role of CD151 in epithelial cell migration. Under standard culture conditions, the migratory capacity of epithelial HaCaT cells on laminins is low, apparently due to endogenous laminin 5. However, challenging HaCaT cells with TS151r allows a rearrangement of the actin cytoskeleton, dismantling of cell-cell and beta 4 integrin-mediated cell-matrix contacts and cell migration. In vivo, free CD151 is absent in resting epithelial cells of interfollicular epidermis, and all CD151 is bound to integrins in intercellular and cell-matrix contacts. By contrast, free CD151 is present at intercellular contacts in the epithelial sheet lining the deeper region of anagen hair follicles, which is considered to contain migrating cells. Together, these results strongly suggest that dissociation of the CD151-integrin complex permits remodeling of epithelial cell interactions with the extracellular matrix and cell migration. (c) 2006 Elsevier Inc. All rights reserved.