CD98 modulates integrin β1 function in polarized epithelial cells
CD98 modulates integrin β1 function in polarized epithelial cells
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DOI：
10.1242/jcs.01674
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发表时间：
2005-03-01
影响因子：
4
通讯作者：
Zent, R
中科院分区：
文献类型：
--
作者：
Cai, S;Bulus, N;Zent, R
II型跨膜蛋白CD 98，作为异二聚体氨基酸转运蛋白（HAT）的重链而闻名，是极化上皮细胞中该转运蛋白复合物的表面表达和基底外侧定位所必需的。CD 98还与I整联蛋白相互作用，导致其对配体的亲和力增加。在这项研究中，我们探讨了CD 98的跨膜和胞质结构域的整合素依赖的细胞粘附和迁移极化肾上皮细胞的作用。我们证明了CD 98的跨膜结构域是足够的，而该结构域的5个N-末端氨基酸是CD 98与β 1整合素相互作用所需的。无论是全长CD 98或CD 98缺乏其胞质尾的过表达增加细胞粘附和迁移，而删除的5个N-末端氨基酸的跨膜结构域的CD 98废除这种效果。与β 1整合素相互作用的CD 98和突变体增加粘着斑形成和FAK和AKT磷酸化。CD 98诱导的细胞粘附和迁移被磷酸肌醇3-OH激酶（PI 3-K）抑制剂抑制，表明这些细胞功能是PI 3-K依赖性的。最后，CD 98和与PI相互作用的突变体诱导胶原凝胶中极化肾上皮细胞分支形态发生的显著变化。因此，在极化的肾上皮细胞中，CD 98可被视为支架蛋白，其与基底外侧表达的氨基酸转运蛋白和β 1整联蛋白相互作用，并可改变多种细胞功能，如氨基酸转运以及细胞粘附、迁移和分支形态发生。
The type II transmembrane protein CD98, best known as the heavy chain of the heterodimeric amino acid transporters (HAT), is required for the surface expression and basolateral localization of this transporter complex in polarized epithelial cells. CD98 also interacts with I integrins resulting in an increase in their affinity for ligand. In this study we explored the role of the transmembrane and cytoplasmic domains of CD98 on integrin-dependent cell adhesion and migration in polarized renal epithelial cells. We demonstrate that the transmembrane domain of CD98 was sufficient, whereas the five N-terminal amino acids of this domain were required for CD98 interactions with beta 1 integrins. Overexpression of either full-length CD98 or CD98 lacking its cytoplasmic tail increased cell adhesion and migration, whereas deletion of the five N-terminal amino acids of the transmembrane domain of CD98 abrogated this effect. CD98 and mutants that interacted with beta 1 integrins increased both focal adhesion formation and FAK and AKT phosphorylation. CD98-induced cell adhesion and migration was inhibited by addition of phosphoinositol 3-OH kinase (PI3-K) inhibitors suggesting these cell functions are PI3-K-dependent. Finally, CD98 and mutants that interacted with PI, induced marked changes in polarized renal epithelia] cell branching morphogenesis in collagen gels. Thus, in polarized renal epithelial cells, CD98 might be viewed as a scaffolding protein that interacts with basolaterally expressed amino acid transporters and beta 1 integrins and can alter diverse cellular functions such as amino acid transport as well as cell adhesion, migration and branching morphogenesis.