Characterization of the osteoblast-specific transmembrane protein IFITM5 and analysis of IFITM5-deficient mice

Abstract

Interferon-inducible transmembrane protein 5 (IFITM5) is an osteoblast-specific membrane protein whose expression peaks around the early mineralization stage during the osteoblast maturation process. To investigate IFITM5 function, we first sought to identify which proteins interact with IFITM5. Liquid chromatography mass spectrometry revealed that FK506-binding protein 11 (FKBP11) co-immunoprecipitated with IFITM5. FKBP11 is the only protein it was found to interact with in osteoblasts, while IFITM5 interacts with several proteins in fibroblasts. FKBPs are involved in protein folding and immunosuppressant binding, but we could not be sure that IFITM5 participated in these activities when bound to FKBP11. Thus, we generated Ifitm5-deficient mice and analyzed their skeletal phenotypes. The skeletons, especially the long bones, of homozygous mutants (Ifitm5(-/-)) were smaller than those of heterozygous mutants (Ifitm5(+/-)), although we did not observe any significant differences in bone morphometric parameters. The effect of Ifitm5 deficiency on bone formation was more significant in newborns than in young and adult mice, suggesting that Ifitm5 deficiency might have a greater effect on prenatal bone development. Overall, the effect of Ifitm5 deficiency on bone formation was less than we expected. We hypothesize that this may have resulted from a compensatory mechanism in Ifitm5-deficient mice.

Effects of targeted modulation of miR-762 on expression of the IFITM5 gene in Saos-2 cells

“…Overexpression of IFITM5 in osteoblasts results in increased mineralization in vitro (13) and in the current study a low level of miR-762 in Saos-2 cells increased the expression of IFITM5, which may possibly contribute to hyperplastic callus formation. Furthermore, FK506-binding protein 11 (FKBP11) was identified as the only known binding partner of IFITM5 (27). Recent studies have revealed that the S-palmitoylation on IFITM5 promotes interaction with FKBP11 and cumulatively forms IFITM5-FKBP11-CD81, the prostaglandin F2 receptor negative regulator (FPRP) complex.…”

New Aspects of Genetic Basis, Classification and Treatment of Osteogenesis Imperfecta: Literature Review

“…Вероятнее всего, данный белок участвует в формиро-вании костной ткани в эмбриональном периоде. Также в исследованиях было описано, что IFITM5 участву-ет не только в формировании костной ткани, но также в формировании иммунной системы [19].…”

Identification of the Polymorphisms in IFITM2 and IFITM5 Genes and their Association with Ulcerative Colitis

“…Expression levels of IFITM genes have been found to be up-regulated in gastric cancer cells and colorectal tumors [4,29]. The IFITM family potently inhibits human immunodeficiency virus type 1 (HIV-1) [23], SARS coronavirus [16], West Nile virus and dengue virus infections [12]. IFITM1 was initially cloned from a human lymphoid cell cDNA library [15], and is located on chromosome 11p15.5 [24].…”