Rap1A-deficient T and B cells show impaired integrin-mediated cell adhesion
Rap1A-deficient T and B cells show impaired integrin-mediated cell adhesion
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DOI：
10.1128/mcb.26.2.643-653.2006
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发表时间：
2006-01-01
影响因子：
5.3
通讯作者：
Zwartkiruis, FJT
中科院分区：
文献类型：
--
作者：
Duchniewicz, M;Zemojtel, T;Zwartkiruis, FJT
在组织培养细胞中的研究已经证明Ras样GTdR Rapt在调节整合素介导的细胞-基质和钙粘蛋白介导的细胞-细胞接触中的作用。为了分析Rap 1在体内的功能，我们通过同源重组破坏了Rap 1A基因。缺失等位基因纯合的小鼠是可存活和可生育的。然而，从脾或胸腺分离的原代造血细胞对ICAM和纤连蛋白底物的粘附能力降低。此外，与野生型细胞相比，CD 3刺激后Rap 1（-/-）细胞的T细胞极化受损。尽管如此，这些缺陷并没有导致造血或细胞归巢异常。虽然这是可能的，相对温和的表型是由Rap 1B基因的功能互补的结果，我们的遗传研究证实了Rap 1A在整联蛋白的调节作用。
Studies in tissue culture cells have demonstrated a role for the Ras-like GTPase Rapt in the regulation of integrin-mediated cell-matrix and cadherin-mediated cell-cell contacts. To analyze the function of Rap1 in vivo, we have disrupted the Rap1A gene by homologous recombination. Mice homozygous for the deletion allele are viable and fertile. However, primary hematopoietic cells isolated from spleen or thymus have a diminished adhesive capacity on ICAM and fibronectin substrates. In addition, polarization of T cells from Rap1(-/-) cells after CD3 stimulation was impaired compared to that of wild-type cells. Despite this, these defects did not result in hematopoietic or cell homing abnormalities. Although it is possible that the relatively mild phenotype is a consequence of functional complementation by the Rap1B gene, our genetic studies confirm a role for Rap1A in the regulation of integrins.