Palladin regulates cell and extracellular matrix interaction through maintaining normal actin cytoskeleton architecture and stabilizing beta1-integrin
Palladin regulates cell and extracellular matrix interaction through maintaining normal actin cytoskeleton architecture and stabilizing beta1-integrin
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DOI：
10.1002/jcb.21126
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发表时间：
2007-04-01
影响因子：
4
通讯作者：
Wang, Zhu-Gang
中科院分区：
文献类型：
--
作者：
Liu, Xue-Song;Luo, Hui-Jun;Wang, Zhu-Gang
细胞和细胞外基质（ECM）的相互作用在发育和正常细胞功能中起着重要作用。细胞在ECM上的粘附和铺展是细胞与ECM相互作用的两种基本细胞行为。在这里，我们表明，palladin，一种新的肌动蛋白细胞外基质相关蛋白，积极参与细胞-ECM相互作用的调节。研究发现，palladin缺陷的小鼠胚胎成纤维细胞（MEFs）在各种ECM上显示出细胞粘附力降低和细胞铺展受损。在palladin（-/-）MEFs中，以微弱的应力纤维、较少的片状伪足和局灶性粘附为特征的紊乱的肌动蛋白细胞骨架结构可以解释细胞-ECM相互作用减弱的原因。此外，在palladin（-/-）MEF中可以观察到聚合丝肌动蛋白减少和球状肌动蛋白增加，这强烈表明palladin对于聚合丝肌动蛋白的形成或稳定至关重要。palladin（-/-）MEFs中磷酸化cofilin水平升高和cofilin磷酸化对Rho信号激动剂或拮抗剂的适当响应表明palladin（-/-）MEFs中破坏的应力纤维与cofilin磷酸化无关。更有趣的是，ECM受体β 1-整联蛋白的蛋白质水平在缺乏palladin的MEFs中显著降低。β 1-整联蛋白的下调可以通过蛋白酶体抑制剂MG-132治疗恢复。所有这些数据暗示palladin通过维持正常的肌动蛋白细胞骨架结构和稳定β 1-整合素蛋白在细胞-ECM相互作用中是必需的。
Cell and extracellular matrix (ECM) interaction plays an important role in development and normal cellular function. Cell adhesion and cell spreading on ECM are two basic cellular behaviors related to cell-ECM interaction. Here we show that palladin, a novel actin cytoskeleton-associated protein, is actively involved in the regulation of cell-ECM inte'raction. It was found that palladin-deficient mouse embryonic fibroblasts (MEFs) display decreased cell adhesion and compromised cell spreading on various ECMs. Disorganized actin cytoskeleton architecture characterized by faint stress fibers, less lamellipodia and focal adhesions can account for the weakened cell-ECM interaction in palladin(-/-) MEFs. Furthermore, decreased polymerized filament actin and increased globular actin can be observed in palladin(-/-) MEFs, strongly suggesting that palladin is essential for the formation or stabilization of polymerized filament actin. Elevated phospho-cofilin level and proper responses in cofilin phosphorylation to either Rho signal agonist or antagonist in palladin(-/-) MEFs indicate that disrupted stress fibers in palladin(-/-) MEFs is not associated with cofilin phosphorylation. More interestingly, the protein level of ECM receptor beta 1-integrin is dramatically decreased in MEFs lacking palladin. Down-regulation of beta 1-integrin protein can be restored by proteasome inhibitor MG-132 treatment. All these data implicate that palladin is essential for cell-ECM interaction through maintaining normal actin cytoskeleton architecture and stabilizing beta 1-integrin protein.