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首页> 外文期刊>Journal of Cellular Physiology >Dendritic Cell-Specific Transmembrane Protein (DC-STAMP) Regulates Osteoclast Differentiation via the Ca2+/NFATc1 Axis
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Dendritic Cell-Specific Transmembrane Protein (DC-STAMP) Regulates Osteoclast Differentiation via the Ca2+/NFATc1 Axis

机译：树突特异性跨膜蛋白(DC-STAMP)调节破骨细胞分化通过Ca2 + / NFATc1轴

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DC-STAMP is a multi-pass transmembrane protein essential for cell-cell fusion between osteoclast precursors during osteoclast (OC) development. DC-STAMP-/- mice have mild osteopetrosis and form mononuclear cells with limited resorption capacity. The identification of an Immunoreceptor Tyrosine-based Inhibitory Motif (ITIM) on the cytoplasmic tail of DC-STAMP suggested a potential signaling function. The absence of a known DC-STAMP ligand, however, has hindered the elucidation of downstream signaling pathways. To address this problem, we engineered a light-activatable DC-STAMP chimeric molecule in which light exposure mimics ligand engagement that can be traced by downstream Ca2+ signaling. Deletion of the cytoplasmic ITIM resulted in a significant elevation in the amplitude and duration of intracellular Ca2+ flux. Decreased NFATc1 expression in DC-STAMP-/- cells was restored by DC-STAMP over-expression. Multiple biological phenotypes including cell-cell fusion, bone erosion, cell mobility, DC-STAMP cell surface distribution, and NFATc1 nuclear translocation were altered by deletion of the ITIM and adjacent amino acids. In contrast, mutations on each of the tyrosine residues surrounding the ITIM showed no effect on DC-STAMP function. Collectively, our results suggest that the ITIM on DC-STAMP is a functional motif that regulates osteoclast differentiation through the NFATc1/Ca2+ axis. (C) 2016 Wiley Periodicals, Inc.
机译：DC-STAMP多次跨膜蛋白基本信息破骨细胞之间的融合在破骨细胞前体(OC)的发展。DC-STAMP - / -小鼠有轻微的骨硬化病和形式单核细胞吸收有限能力。Tyrosine-based抑制主题(ITIM)胞质尾DC-STAMP建议潜在的信号功能。然而,已知DC-STAMP配体已经阻碍了说明的下游信号通路。解决这一问题,我们设计了一个light-activatable DC-STAMP嵌合分子曝光模仿配体参与这可以通过下游Ca2 +跟踪信号。删除细胞质ITIM导致的重要的振幅和海拔细胞内钙离子通量的持续时间。NFATc1 DC-STAMP - / -细胞中表达恢复了DC-STAMP表达。生物表型包括信息融合,骨流失,细胞迁移,DC-STAMP细胞表面分布,NFATc1核易位被删除的改变ITIM和相邻的氨基酸。每个酪氨酸残基的突变对DC-STAMP ITIM周围没有影响函数。ITIM DC-STAMP是功能主题调节破骨细胞分化的NFATc1 / Ca2 +轴。公司。

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