Silencing of VAMP3 inhibits cell migration and integrin-mediated adhesion.

Silencing of VAMP3 inhibits cell migration and integrin-mediated adhesion.
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VAMP3的沉默抑制细胞迁移和整联蛋白介导的粘附。

DOI:
10.1016/j.bbrc.2009.01.036
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发表时间:
2009-02-27
影响因子:
3.1
通讯作者:
Hu, Chuan
Hu, Chuan
中科院分区:
生物学4区
文献类型:
--
作者:
Luftman, Kevin;Hasan, Nazarul;Day, Paul;Hardee, Deborah;Hu, Chuan

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整合素是细胞与细胞外基质黏附的跨膜受体。在细胞迁移过程中,整合素从细胞膜或细胞表面被内吞,以小泡的形式运输,并在细胞前沿主动地排出。在目前的研究中,我们研究了VAMP3,一种介导胞吐作用的SNARE蛋白,在细胞迁移和整合素运输中的作用。小干扰RNA(SiRNA)诱导的VAMP3沉默可在不影响细胞增殖的情况下抑制60%以上的趋化细胞迁移。VAMP3沉默使细胞表面β1整合素水平降低,但对细胞总β1整合素水平无影响,提示VAMP3是β1整合素转运至细胞膜的必需分子。此外,VAMP3沉默降低了细胞与层粘连蛋白的粘附性,但不会减少细胞与纤维连接蛋白或胶原的粘附性。综上所述,这些数据表明,依赖VAMP3的整合素运输在细胞迁移和细胞与层粘连蛋白的黏附中起着至关重要的作用。
Integrins are transmembrane receptors for cell adhesion to the extracellular matrix. In cell migration, integrins are endocytosed from the plasma membrane or the cell surface, transported in vesicles and exocytosed actively at the cell front. In the current study, we examined the roles of VAMP3, a SNARE protein that mediates exocytosis, in cell migration and integrin trafficking. Small interfering RNA (siRNA)-induced silencing of VAMP3 inhibited chemotactic cell migration by more than 60% without affecting cell proliferation. VAMP3 silencing reduced the levels of β1 integrin at the cell surface but had no effect on total cellular β1 integrin, indicating that VAMP3 is required for trafficking of β1 integrin to the plasma membrane. Furthermore, VAMP3 silencing diminished cell adhesion to laminin but not to fibronectin or collagen. Taken together, these data suggest that VAMP3-dependent integrin trafficking is crucial in cell migration and cell adhesion to laminin.
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