Characterization of the osteoblast-specific transmembrane protein IFITM5 and analysis of IFITM5-deficient mice.
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.
Hanagata
Nobutaka
N
Nanotechnology Innovation Center, National Institute for Materials Science, 1-2-1 Sengen, Tsukuba, Ibaraki 305-0047, Japan. HANAGATA.Nobutaka@nims.go.jp
Li
Xianglan
X
Morita
Hiromi
H
Takemura
Taro
T
Li
Jie
J
Minowa
Takashi
T
D000818:Animals; D000831:Animals, Newborn; D001842:Bone and Bones / Q000378:metabolism; D002113:Calcification, Physiologic; D004622:Embryo, Mammalian / Q000166:cytology / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D055786:Gene Knockout Techniques; D006579:Heterozygote; D006720:Homozygote; D008565:Membrane Proteins / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D009929:Organ Size; D009928:Organ Specificity; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism*; D010641:Phenotype; D011485:Protein Binding; D034443:RNA Transport; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D022021:Tacrolimus Binding Proteins / Q000378:metabolism
C532488:IFITM5 protein, mouse; D008565:Membrane Proteins; D012333:RNA, Messenger; D022021:Tacrolimus Binding Proteins