BACKGROUND Transmembrane and immunoglobulin domain-containing protein 1 (TMIGD1) is a recently identified cell adhesion molecule which is predominantly expressed by epithelial cells of the intestine and the kidney. Its expression is downregulated in both colon and renal cancer suggesting a tumor suppressive activity. The function of TMIGD1 at the cellular level is largely unclear. Published work suggests a protective role of TMIGD1 during oxidative stress in kidney epithelial cells, but the underlying molecular mechanisms are unknown. RESULTS In this study, we address the subcellular localization of TMIGD1 in renal epithelial cells and identify a cytoplasmic scaffold protein as interaction partner of TMIGD1. We find that TMIGD1 localizes to different compartments in renal epithelial cells and that this localization is regulated by cell confluency. Whereas it localizes to mitochondria in subconfluent cells it is localized at cell-cell contacts in confluent cells. We find that cell-cell contact localization is regulated by N-glycosylation and that both the extracellular and the cytoplasmic domain contribute to this localization. We identify Synaptojanin 2-binding protein (SYNJ2BP), a PDZ domain-containing cytoplasmic protein, which localizes to both mitochondria and the plasma membrane, as interaction partner of TMIGD1. The interaction of TMIGD1 and SYNJ2BP is mediated by the PDZ domain of SYNJ2BP and the C-terminal PDZ domain-binding motif of TMIGD1. We also find that SYNJ2BP can actively recruit TMIGD1 to mitochondria providing a potential mechanism for the localization of TMIGD1 at mitochondria. CONCLUSIONS This study describes TMIGD1 as an adhesion receptor that can localize to both mitochondria and cell-cell junctions in renal epithelial cells. It identifies SYNJ2BP as an interaction partner of TMIGD1 providing a potential mechanism underlying the localization of TMIGD1 at mitochondria. The study thus lays the basis for a better understanding of the molecular function of TMIGD1 during oxidative stress regulation.

中文翻译：

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线粒体外膜蛋白SYNJ2BP与细胞粘附分子TMIGD1相互作用，可以将其募集到线粒体中。

背景技术跨膜和含免疫球蛋白结构域的蛋白1（TMIGD1）是最近鉴定出的细胞粘附分子，其主要由肠和肾的上皮细胞表达。它的表达在结肠癌和肾癌中均被下调，表明具有肿瘤抑制活性。TMIGD1在细胞水平上的功能尚不清楚。发表的工作表明TMIGD1在肾脏上皮细胞氧化应激中的保护作用，但潜在的分子机制尚不清楚。结果在这项研究中，我们解决了TMIGD1在肾上皮细胞中的亚细胞定位，并确定了细胞质支架蛋白作为TMIGD1的相互作用伴侣。我们发现TMIGD1定位于肾上皮细胞的不同区室，并且这种定位受细胞融合的调节。它位于亚汇合细胞中的线粒体，而位于汇合细胞中的细胞间接触处。我们发现细胞间的接触定位受N-糖基化的调节，并且细胞外和细胞质域都有助于这种定位。我们确定Synaptojanin 2结合蛋白（SYNJ2BP），一个PDZ域包含细胞质蛋白，定位到线粒体和质膜，作为TMIGD1的相互作用伙伴。TMIGD1和SYNJ2BP的相互作用由SYNJ2BP的PDZ域和TMIGD1的C端PDZ域结合基序介导。我们还发现SYNJ2BP可以积极招募TMIGD1到线粒体，为TMIGD1在线粒体中定位提供了潜在的机制。结论这项研究将TMIGD1描述为一种粘附受体，可以定位于肾上皮细胞的线粒体和细胞间连接处。它确定SYNJ2BP为TMIGD1的相互作用伙伴，为TMIGD1定位于线粒体提供了潜在的机制。因此，该研究为更好地理解TMIGD1在氧化应激调节过程中的分子功能奠定了基础。