PDF(Pubmed)
Abstract：
Invariant chain (Ii, CD74) is a type II transmembrane glycoprotein that acts as a chaperone and facilitates the folding and transport of MHC II chains. By assisting the assembly and subcellular targeting of MHC II complexes, Ii has a wide impact on the functions of antigen-presenting cells such as antigen processing, endocytic maturation, signal transduction, cell migration, and macropinocytosis. Ii is a multifunctional molecule that can alter endocytic traffic and has several interacting molecules. To understand more about Ii\'s function and to identify further Ii interactors, a yeast two-hybrid screening was performed. Retinoic Acid-Induced 14 (Rai14) was detected as a putative interaction partner, and the interaction was confirmed by co-immunoprecipitation. Rai14 is a poorly characterized protein, which is believed to have a role in actin cytoskeleton and membrane remodeling. In line with this, we found that Rai14 localizes to membrane ruffles, where it forms macropinosomes. Depletion of Rai14 in antigen-presenting cells delays MHC II internalization, affecting macropinocytic activity. Intriguingly, we demonstrated that, similar to Ii, Rai14 is a positive regulator of macropinocytosis and a negative regulator of cell migration, two antagonistic processes in antigen-presenting cells. This antagonism is known to depend on the interaction between myosin II and Ii. Here, we show that Rai14 also binds to myosin II, suggesting that Ii, myosin II, and Rai14 work together to coordinate macropinocytosis and cell motility.
摘要：
不变链(Ii，CD74）是一种II型跨膜糖蛋白，充当伴侣，促进MHCII链的折叠和转运。通过协助MHCII复合物的组装和亚细胞靶向，II对抗原呈递细胞的功能有广泛的影响，如抗原加工，胞吞成熟,信号转导，细胞迁移，和巨细胞增多症。Ii是一种多功能分子，可以改变胞吞运输，并具有几个相互作用的分子。要更多地了解Ii的功能并确定更多的Ii交互者，进行了酵母双杂交筛选.视黄酸诱导的14（Rai14）被检测为推定的相互作用伴侣，并且通过免疫共沉淀证实了相互作用。Rai14是一种特征不佳的蛋白质，它被认为在肌动蛋白细胞骨架和膜重塑中起作用。与此相符,我们发现Rai14位于膜荷叶边，在那里它形成大黄体。抗原呈递细胞中Rai14的耗尽延迟了MHCII内化，影响巨噬细胞活动。有趣的是，我们证明了，类似于Ii,Rai14是巨噬细胞增多的正调节因子和细胞迁移的负调节因子，抗原呈递细胞中的两个拮抗过程。已知这种拮抗作用取决于肌球蛋白II和Ii之间的相互作用。这里,我们显示Rai14也与肌球蛋白II结合，暗示Ii，肌球蛋白II,和Rai14一起工作以协调巨噬细胞增多和细胞运动。
