Nuclear localization of DMP1 proteins suggests a role in intracellular signaling.
Dentin matrix protein 1 (DMP1) is highly expressed in odontoblasts and osteoblasts/osteocytes and plays an essential role in tooth and bone mineralization and phosphate homeostasis. It is debatable whether DMP1, in addition to its function in the extracellular matrix, can enter the nucleus and function as a transcription factor. To better understand its function, we examined the nuclear localization of endogenous and exogenous DMP1 in C3H10T1/2 mesenchymal cells, MC3T3-E1 preosteoblast cells and 17IIA11 odontoblast-like cells. RT-PCR analyses showed the expression of endogenous Dmp1 in all three cell lines, while Western-blot analysis detected a major DMP1 protein band corresponding to the 57 kDa C-terminal fragment generated by proteolytic processing of the secreted full-length DMP1. Immunofluorescent staining demonstrated that non-synchronized cells presented two subpopulations with either nuclear or cytoplasmic localization of endogenous DMP1. In addition, cells transfected with a construct expressing HA-tagged full-length DMP1 also showed either nuclear or cytoplasmic localization of the exogenous DMP1 when examined with an antibody against the HA tag. Furthermore, nuclear DMP1 was restricted to the nucleoplasm but was absent in the nucleolus. In conclusion, these findings suggest that, apart from its role as a constituent of dentin and bone matrix, DMP1 might play a regulatory role in the nucleus.
Department of Biomedical Sciences, Baylor College of Dentistry, Texas A&M Health Science Center, 3302 Gaston Ave., Dallas, TX 75246-2013, United States.
Arwa
A
Siyam
Suzhen
S
Wang
Chunlin
C
Qin
Gabriele
G
Mues
Roy
R
Stevens
Rena N
RN
D'Souza
Yongbo
Y
Lu
D016475:3T3 Cells; D021581:Active Transport, Cell Nucleus; D000818:Animals; D019556:COS Cells; D002467:Cell Nucleus / Q000378:metabolism*; D002522:Chlorocebus aethiops; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D051379:Mice; D010006:Osteoblasts / Q000378:metabolism; D015398:Signal Transduction
C513308:Dmp1 protein, mouse; D016326:Extracellular Matrix Proteins