Transmernbrane CEACAM1 affects integrin-dependent signaling and regulates extracellular matrix protein-specific morphology and migration of endothelial cells
Transmernbrane CEACAM1 affects integrin-dependent signaling and regulates extracellular matrix protein-specific morphology and migration of endothelial cells
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DOI：
10.1182/blood-2004-09-3618
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发表时间：
2005-05-15
期刊：
影响因子：
20.3
通讯作者：
Lucka, L
中科院分区：
文献类型：
--
作者：
Müller, MM;Singer, BB;Lucka, L
癌胚抗原相关细胞粘附分子1 (CEACAM1/CD66a)，表达于白细胞、上皮和内皮细胞，介导嗜同性细胞粘附。它在细胞形态发生中起着重要作用，最近，可溶性CEACAM1亚型与血管生成有关。在本研究中，我们研究了CEACAM1长跨膜异构体（CEACAM1- l）在培养的大鼠脑内皮细胞中的功能。我们观察到CEACAM1-L的表达促进了基底膜基质上的网络形成，并增加了单层损伤后细胞的运动性。在细胞-基质粘附过程中，CEACAM1-L易位到Triton x -100不溶性细胞骨架部分，并影响Matrigel和laminin-1上的细胞扩散和细胞形态，但不影响纤维连接蛋白。在层粘连蛋白-1上，表达ceacam1 - l的细胞出现带板足的突起，应力纤维形成减少，局灶粘连激酶（FAK）酪氨酸磷酸化减少，局灶粘连形成减少，导致高运动性。通过溶血磷脂酸（LPA）处理，ceacam1 - l介导的形态学改变对RhoA激活敏感，并依赖于Rac1激活。此外，我们证明了CEACAM1-L与talin（整合素功能的重要调节因子）的基质蛋白依赖性关联。综上所述，我们的研究结果表明，内皮细胞上跨膜表达的CEACAM1-L通过影响细胞骨架结构和整合素介导的信号传导参与了血管生成的激活阶段。
Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1/CD66a), expressed on leukocytes, epithelia, and endothelia mediates homophilic cell adhesion. It plays an important role in cell morphogenesis and, recently, soluble CEACAM1 isoforms have been implicated in angiogenesis. In the present study, we investigated the function of long transmembrane isoform of CEACAM1 (CEACAM1-L) in cultured rat brain endothelial cells. We observed that expression of CEACAM1-L promotes network formation on basement membrane Matrigel and increased cell motility after monolayer injury. During cell-matrix adhesion, CEACAM1-L translocated into the Triton X-100-insoluble cytoskeletal fraction and affected cell spreading and cell morphology on Matrigel and laminin-1 but not on fibronectin. On laminin-1, CEACAM1-L-expressing cells developed protrusions with lamellipodia, showed less stress fiber formation, reduced focal adhesion kinase (FAK) tyrosine phosphorylation, and decreased focal adhesion formation leading to high motility. CEACAM1-L-mediated morphologic alterations were sensitive to RhoA activation via lysophosphatidic acid (LPA) treatment and dependent on Rac1 activation. Furthermore, we demonstrate a matrix protein-dependent, association of CEACAM1-L with talin, an important regulator of integrin function. Taken together, our results suggest that transmembrane CEACAM1-L expressed on endothelial cells is implicated in the activation phase of angiogenesis by affecting the cytoskeleton architecture and integrin-mediated signaling.