The roles of two distinct regions of PINCH-1 in the regulation of cell attachment and spreading.
The roles of two distinct regions of PINCH-1 in the regulation of cell attachment and spreading.
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DOI：
10.1091/mbc.e10-05-0459
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发表时间：
2010-12
影响因子：
3.3
通讯作者：
Senga T
中科院分区：
文献类型：
--
作者：
Ito S;Takahara Y;Hyodo T;Hasegawa H;Asano E;Hamaguchi M;Senga T
PINCH-1由5个LIM结构域和C-末端区域组成，对于调节细胞-ECM粘附至关重要。LIM1结构域是细胞附着所必需的，而C-末端区域是细胞通过介导与Rsu-1的关联而扩散所必需的。PINCH-1-Rsu-1通路激活Rac以促进细胞铺展。细胞通过整合素附着到细胞外基质（ECM）上以形成粘着斑复合物，并且该过程之后是板状伪足的延伸以使细胞扩散。PINCH-1是一种调节细胞-ECM粘附所必需的衔接蛋白，由五个串联的LIM结构域和一个小的C-末端区域组成。已知PINCH-1与整合素连接激酶（ILK）和Ras抑制蛋白1（Rsu-1）相互作用;然而，该复合物调节细胞-ECM粘附的确切机制尚未完全了解。我们在这里报告的LIM1结构域的PINCH-1，它与ILK，以稳定这种蛋白质的表达，是足够的细胞附着，但不为细胞扩散。与此相反，PINCH-1的C-末端区域与Rsu-1结合，在细胞铺展中起关键作用，但在细胞附着中不起关键作用。我们还表明，PINCH-1协会与Rsu-1激活Rac1和Rac1激活是必要的细胞扩散。因此，这些数据揭示了PINCH-1的特定结构域如何指导两个独立的途径：一个利用ILK允许细胞附着，另一个招募Rsu-1激活Rac 1以促进细胞扩散。
PINCH-1, which comprises five LIM domains and the C-terminal region, is crucial for the regulation of cell–ECM adhesion. The LIM1 domain is essential for cell attachment, whereas C-terminal region is required for cell spreading by mediating the association with Rsu-1. PINCH-1–Rsu-1 pathway activates Rac to promote cell spreading. Cells attach to the extracellular matrix (ECM) through integrins to form focal adhesion complexes, and this process is followed by the extension of lamellipodia to enable cell spreading. PINCH-1, an adaptor protein essential for the regulation of cell–ECM adhesion, consists of five tandem LIM domains and a small C-terminal region. PINCH-1 is known to interact with integrin-linked kinase (ILK) and Ras suppressor protein 1 (Rsu-1); however, the precise mechanism by which this complex regulates cell–ECM adhesion is not fully understood. We report here that the LIM1 domain of PINCH-1, which associates with ILK to stabilize the expression of this protein, is sufficient for cell attachment but not for cell spreading. In contrast, the C-terminal region of PINCH-1, which binds to Rsu-1, plays a pivotal role in cell spreading but not in cell attachment. We also show that PINCH-1 associates with Rsu-1 to activate Rac1 and that Rac1 activation is necessary for cell spreading. Thus, these data reveal how specific domains of PINCH-1 direct two independent pathways: one utilizing ILK to allow cell attachment, and the other recruiting Rsu-1 to activate Rac1 in order to promote cell spreading.