Interdisciplinary Laboratory for Nanoscale Science and Technology, National Institute for Materials Science, 1-2-1 Sengen, Tsukuba, Ibaraki 305-0047, Japan.
Biochem Biophys Res Commun. 2011 Jun 10;409(3):378-84. doi: 10.1016/j.bbrc.2011.04.136. Epub 2011 May 11.
Osteoblasts are rich in interferon-inducible transmembrane protein 5 (IFITM5), the expression of which peaks around the early mineralization stage. This membrane protein directly associates with FK506 binding protein 11 (FKBP11). To examine the molecular function of IFITM5, we analyzed the protein interaction network around IFITM5-FKBP11. We found that FKBP11 was associated with CD81, which interacts with prostaglandin F2 receptor negative regulator (FPRP) and CD9; cumulatively, these associations result in the formation of a FKBP11-CD81-[FPRP/CD9] complex. However, CD9 dissociated from the complex following expression of Ifitm5, which also led to osteoblast-specific increased expression of 5 interferon-induced genes: bone marrow stromal cell antigen 2 (Bst2), interferon inducible protein 1 (Irgm), interferon-induced protein with tetratricopeptide repeats 3 (Ifit3), b(2)-microglobulin (B2m), and MHC (A.CA/J(H-2K-f) class I antigen gene. Induction of these genes likely resulted from dissociation of CD9 from the FKBP11-CD81-[FPRP/CD9] complex. Cumulatively, these results suggest that IFITM5 is involved not only in bone formation, but also in immune system activity.
成骨细胞富含干扰素诱导跨膜蛋白 5（IFITM5），其表达在早期矿化阶段达到峰值。这种膜蛋白直接与 FK506 结合蛋白 11（FKBP11）结合。为了研究 IFITM5 的分子功能，我们分析了 IFITM5-FKBP11 周围的蛋白质相互作用网络。我们发现 FKBP11 与 CD81 相关，CD81 与前列腺素 F2 受体负调节剂（FPRP）和 CD9 相互作用；这些相互作用累积导致 FKBP11-CD81-[FPRP/CD9] 复合物的形成。然而，CD9 在表达 Ifitm5 后从复合物中解离，这也导致成骨细胞中 5 种干扰素诱导基因的特异性表达增加：骨髓基质细胞抗原 2（Bst2）、干扰素诱导蛋白 1（Irgm）、干扰素诱导的具有四肽重复 3（Ifit3）、β2-微球蛋白（B2m）和 MHC（A.CA/J（H-2K-f）I 类抗原基因。这些基因的诱导可能是由于 CD9 从 FKBP11-CD81-[FPRP/CD9] 复合物中解离。总之，这些结果表明 IFITM5 不仅参与骨形成，还参与免疫系统活性。
