New insights on membrane mediated effects of 1α,25-dihydroxy vitamin D3 signaling in the musculoskeletal system
New insights on membrane mediated effects of 1α,25-dihydroxy vitamin D3 signaling in the musculoskeletal system
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DOI：
10.1016/j.steroids.2013.10.019
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发表时间：
2014-03-01
期刊：
影响因子：
2.7
通讯作者：
Schwartz, Zvi
中科院分区：
文献类型：
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作者：
Doroudi, Maryam;Chen, Jiaxuan;Schwartz, Zvi
1 α，25-二羟基维生素D3 [1 α，25（OH）（2）D-3]通过经典类固醇激素受体介导的基因转录和启动快速膜介导的信号传导途径作用于细胞。两种受体在1 α，25（OH）（2）D-3介导的快速信号传导中起作用，经典的核维生素D受体（VDR）和蛋白质二硫键异构酶，家族A，成员3（Pdia 3）。对这两种受体作用的长期研究表明，Pdia 3位于细胞膜小窝，在那里它与磷脂酶A2（PLA 2）激活蛋白（PLAA）和小窝蛋白-1（Cav-1）相互作用，通过Ca++/钙调蛋白依赖性蛋白激酶II（CaMK II）、PLA 2、磷脂酶C（PLC）、蛋白激酶C（PKC）、最终是丝裂原活化蛋白激酶（MAPK）的ERK 1/2家族。VDR存在于质膜上，并且它是1 α，25（OH）（2）D-3诱导的Src快速活化所必需的。PDIA 3 +/-小鼠表现出受损的肌肉骨骼表型。此外，我们在3D培养中检查前成骨细胞的矿化的研究已经显示了Pdia 3和VDR相互作用的生理重要性：Pdia 3或VDR的敲除的特征在于构建体的矿化受损。(C)2013 Elsevier Inc. All rights reserved.
1 alpha,25-Dihydroxy vitamin D3 [1 alpha,25(OH)(2)D-3] acts on cells via classical steroid hormone receptor-mediated gene transcription and by initiating rapid membrane-mediated signaling pathways. Two receptors have been implicated to play roles in 1 alpha,25(OH)(2)D-3 mediated rapid signaling, the classical nuclear vitamin D receptor (VDR) and protein disulfide isomerase, family A, member 3 (Pdia3). Long term efforts to investigate the roles of these two receptors demonstrated thatPdia3 is located in caveolae, where it interacts with phospholipase A2 (PLA2) activating protein (PLAA) and caveolin-1 (Cav-1) to initiate rapid signaling via Ca++/calmodulin-dependent protein kinase II (CaMKII), PLA2, phospholipase C (PLC), protein kinase C (PKC), and ultimately the ERK1/2 family of mitogen activated protein kinases (MAPK). VDR is present on the plasma membrane, and it is required for 1 alpha,25(OH)(2)D-3 induced rapid activation of Src. PDIA3+/- mice demonstrate an impaired musculoskeletal phenotype. Moreover, our studies examining mineralization of pre-osteoblasts in 3D culture have shown the physiological importance of Pdia3 and VDR interaction: knockdown of Pdia3 or VDR is characterized by impaired mineralization of the constructs. (C) 2013 Elsevier Inc. All rights reserved.