Osteoblast-enriched membrane protein IFITM5 regulates the association of CD9 with an FKBP11-CD81-FPRP complex and stimulates expression of interferon-induced genes.

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.