αII-Spectrin Is Critical for Cell Adhesion and Cell Cycle
αII-Spectrin Is Critical for Cell Adhesion and Cell Cycle
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DOI：
10.1074/jbc.m801324200
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发表时间：
2009-01-23
影响因子：
4.8
通讯作者：
Lecomte, Marie-Christine
中科院分区：
文献类型：
--
作者：
Metral, Sylvain;Machnicka, Beata;Lecomte, Marie-Christine
Spectrin是膜骨架的普遍存在的支架成分，其组织和稳定质膜和细胞内细胞器上的微区。通过与不同蛋白质家族的多种相互作用，它们涉及各种细胞功能。在WM-266细胞系中使用小干扰RNA策略，我们发现α II-血影蛋白缺乏与细胞增殖缺陷相关，这与细胞周期停滞在G（1）期（第一间隙期）有关，如通过DNA分析和Rb磷酸化所评估的。这些观察结果与细胞周期蛋白依赖性激酶抑制剂p21（Cip）的表达升高相吻合。同时，血影蛋白损失损害细胞粘附和扩散。这些细胞粘附缺陷与肌动蛋白细胞骨架的改变有关，如应力纤维的丢失、粘着斑的改变和某些整合素的表达改变。我们的研究结果提供了新的见解血影蛋白的功能，通过展示参与细胞周期调控和肌动蛋白的组织。
Spectrins are ubiquitous scaffolding components of the membrane skeleton that organize and stabilize microdomains on both the plasma membrane and the intracellular organelles. By way of their numerous interactions with diverse protein families, they are implicated in various cellular functions. Using small interfering RNA strategy in the WM-266 cell line derived from human melanoma, we found that alpha II-spectrin deficiency is associated with a defect in cell proliferation, which is related to a cell cycle arrest at the G(1) phase (first gap phase), as evaluated by DNA analysis and Rb phosphorylation. These observations coincided with elevated expression of the cyclin-dependent kinase inhibitor, p21(Cip). Concomitantly, spectrin loss impaired cell adhesion and spreading. These cell adhesion defects were associated with modifications of the actin cytoskeleton, such as loss of stress fibers, alterations of focal adhesions, and modified expression of some integrins. Our results provide novel insights into spectrin functions by demonstrating the involvement of alpha II-spectrin in cell cycle regulation and actin organization.