Epidermal growth factor-induced mobilization of a ganglioside-specific sialidase (NEU3) to membrane ruffles.
Epidermal growth factor-induced mobilization of a ganglioside-specific sialidase (NEU3) to membrane ruffles.
复制标题
DOI：
10.1016/j.bbrc.2006.05.136
复制
发表时间：
2006-07
影响因子：
3.1
通讯作者：
K. Yamaguchi;K. Hata;T. Wada;S. Moriya;T. Miyagi
中科院分区：
文献类型：
--
作者：
K. Yamaguchi;K. Hata;T. Wada;S. Moriya;T. Miyagi
人神经节苷脂特异性唾液酸酶NEU 3定位于细胞膜，被认为调节细胞表面的各种生物学过程。在这里，我们探讨了功能的唾液酸酶的免疫荧光亚细胞定位，并发现积累在细胞膜的前沿存在的血清培养。响应EGF，唾液酸酶迅速重新分布到鳞状细胞癌A431细胞的皱褶细胞膜，并与Rac-1共定位。在HeLa细胞和A431细胞中，与对照相比，NEU 3过表达增强了Rac-1的激活和细胞迁移。与通过免疫荧光与Rac-1的共定位一致，发现NEU 3与结合至GST-PAK-1融合蛋白的活化Rac共沉淀。相反，通过siRNA沉默NEU 3导致Rac-1活化的抑制。这些结果表明，NEU 3能够响应生长刺激而动员到膜皱褶上，并通过与Rac-1共定位来激活Rac-1信号传导，从而导致细胞运动性增加。
Human ganglioside-specific sialidase, NEU3, localized at cell membranes is thought to regulate various biological processes at cell surfaces. We here explored functional subcellular localization of the sialidase by immunofluorescence and found accumulation at leading edges of cell membranes in the presence of serum in culture. In response to EGF, the sialidase redistributed rapidly to ruffling cell membranes of squamous carcinoma A431 cells and co-localized with Rac-1. NEU3 overexpression enhanced Rac-1 activation and cell migration as compared with controls in HeLa cells as well as in A431 cells. Consistent with co-localization with Rac-1 by immunofluorescence, NEU3 was found to co-precipitate with activated Rac bound to GST-PAK-1 fusion protein. NEU3 silencing by siRNA, in contrast, resulted in inhibition of Rac-1 activation. These results indicate that NEU3 is able to mobilize to membrane ruffles in response to growth stimuli and activate the Rac-1 signaling by co-localization with Rac-1, leading to increased cell motility.