Phosphatidic acid regulates subcellular distribution of RA-GEFs critical for chemokine-dependent migration.
Phosphatidic acid regulates subcellular distribution of RA-GEFs critical for chemokine-dependent migration.
复制标题
磷脂酸调节 RA-GEF 的亚细胞分布，这对于趋化因子依赖性迁移至关重要。
DOI：
10.1016/j.bbrc.2020.01.080
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发表时间：
2020
影响因子：
3.1
通讯作者：
Katagiri,Koko
中科院分区：
文献类型：
--
作者：
Momoi,Yasuyuki;Nishikimi,Akihiko;Du,Guangwei;Kataoka,Tohru;Katagiri,Koko
Rap 1-GTP激活整合素是淋巴细胞运输的关键。在这项研究中，我们表明磷脂酸（PA）依赖性膜分布的RA-GEF-1和-2（也称为Rapgef 2和6），这是鸟嘌呤核苷酸交换因子Rap 1，在淋巴细胞迁移中起着重要作用。RA-GEF-1通过CDC 25同源结构域中的919-967 aa与PA结合，RA-GEF-1该区域的缺失抑制了趋化因子依赖的迁移。趋化因子刺激诱导PA在质膜上的暂时产生，这不是Rap 1激活所必需的，而是RA-GEFs的易位。因此，PA的趋化因子依赖性产生是通过RA-GEF的膜定位的淋巴细胞迁移的关键。
Integrin activation by Rap1-GTP is pivotal for lymphocyte trafficking. In this study, we show the phosphatidic acid (PA)-dependent membrane distribution of RA-GEF-1 and -2 (also known as Rapgef2 and 6), which are guanine nucleotide exchange factors for Rap1, plays important roles in lymphocyte migration. RA-GEF-1 associates with PA through 919–967 aa within CDC25 homology domain, and the deletion of this region of RA-GEF-1 inhibits chemokine-dependent migration. Chemokine stimulation induces temporal production of PA on the plasma membrane, which is not necessary for Rap1 activation, but the translocation of RA-GEFs. Thus, chemokine-dependent generation of PA is critical for lymphocyte migration through membrane localization of RA-GEFs.