JAM4, a junctional cell adhesion molecule interacting with a tight junction protein, MAGI-1
JAM4, a junctional cell adhesion molecule interacting with a tight junction protein, MAGI-1
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DOI：
10.1128/mcb.23.12.4267-4282.2003
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发表时间：
2003-06-01
影响因子：
5.3
通讯作者：
Hata, Y
中科院分区：
文献类型：
--
作者：
Hirabayashi, S;Tajima, M;Hata, Y
MAGI-1是上皮细胞紧密连接处的膜相关鸟苷酸激酶蛋白。它与各种分子相互作用，并在细胞连接处作为支架蛋白发挥作用。我们在这里报告一种新的MAGI-1结合蛋白，我们命名为连接粘附分子4（JAM 4）。JAM 4属于免疫球蛋白家族。JAM 4与ZO-1共定位于肾小球和肠上皮细胞中。体外生物化学研究显示，JAM 4结合MAGI-1，但不结合ZO-1，而JAM 1不结合MAGI-1。共表达时，JAM 4和MAGI-1在COS-7细胞中相互作用，形成簇。JAM 4介导钙非依赖性嗜同性粘附，并且当在L细胞中表达时在细胞-细胞接触处积累。将MAGI-1、ZO-1和闭合蛋白募集至基于JAM 4的细胞接触。JAM 4还降低CHO细胞单层的渗透性。MAGI-1增强了L细胞中JAM 4介导的细胞粘附和CHO细胞中的密封效应。这些发现表明，JAM 4与MAGI-1一起在紧密连接处提供粘附机制，其可以调节肾小球和小肠上皮细胞的渗透性。
MAGI-1 is a membrane-associated guanylate kinase protein at tight junctions in epithelial cells. It interacts with various molecules and functions as a scaffold protein at cell junctions. We report here a novel MAGI-1-binding protein that we named junctional adhesion molecule 4 (JAM4). JAM4 belongs to an immunoglobulin protein family. JAM4 was colocalized with ZO-1 in kidney glomeruli and in intestinal epithelial cells. Biochemical in vitro studies revealed that JAM4 bound to MAGI-1 but not to ZO-1, whereas JAM1 did not bind to MAGI-1. JAM4 and MAGI-1 interacted with each other and formed clusters in COS-7 cells when coexpressed. JAM4 mediated calcium-independent homophilic adhesion and was accumulated at cell-cell contacts when expressed in L cells. MAGI-1, ZO-1, and occludin were recruited to JAM4-based cell contacts. JAM4 also reduced the permeability of CHO cell monolayers. MAGI-1 strengthened JAM4-mediated cell adhesion in L cells and sealing effects in CHO cells. These findings suggest that JAM4 together with MAGI-1 provides an adhesion machinery at tight junctions, which may regulate the permeability of kidney glomerulus and small intestinal epithelial cells.