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锌敏感受体(ZnR/GPR39)在健康与疾病中的作用

The Zinc Sensing Receptor, ZnR/GPR39, in Health and Disease.

机构信息

Department of Physiology and Cell Biology and The Zlotowski Center for Neuroscience, Faculty of Health Sciences, POB 653, Ben-Gurion Ave. Ben-Gurion University of the Negev, Beer Sheva 84105, Israel.

出版信息

Int J Mol Sci. 2018 Feb 1;19(2):439. doi: 10.3390/ijms19020439.

DOI:10.3390/ijms19020439
PMID:29389900
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5855661/
Abstract

A distinct G-protein coupled receptor that senses changes in extracellular Zn, ZnR/GPR39, was found in cells from tissues in which Zn plays a physiological role. Most prominently, ZnR/GPR39 activity was described in prostate cancer, skin keratinocytes, and colon epithelial cells, where zinc is essential for cell growth, wound closure, and barrier formation. ZnR/GPR39 activity was also described in neurons that are postsynaptic to vesicular Zn release. Activation of ZnR/GPR39 triggers Gαq-dependent signaling and subsequent cellular pathways associated with cell growth and survival. Furthermore, ZnR/GPR39 was shown to regulate the activity of ion transport mechanisms that are essential for the physiological function of epithelial and neuronal cells. Thus, ZnR/GPR39 provides a unique target for therapeutically modifying the actions of zinc in a specific and selective manner.

摘要

一种能够感知细胞外锌离子变化的独特的 G 蛋白偶联受体(G-protein coupled receptor)ZnR/GPR39 在发挥生理作用的组织细胞中被发现。在前列腺癌、皮肤角质细胞和结肠上皮细胞中,ZnR/GPR39 的活性尤为明显,因为锌对于细胞生长、伤口愈合和屏障形成是必需的。ZnR/GPR39 的活性也在突触后囊泡释放锌的神经元中被描述。ZnR/GPR39 的激活引发 Gαq 依赖性信号转导,以及与细胞生长和存活相关的后续细胞途径。此外,ZnR/GPR39 被证明可以调节离子转运机制的活性,而这些机制对于上皮细胞和神经元细胞的生理功能是必需的。因此,ZnR/GPR39 为以特定和选择性的方式治疗性修饰锌的作用提供了一个独特的靶点。

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Perturbed bone composition and integrity with disorganized osteoblast function in zinc receptor/Gpr39-deficient mice.锌受体/Gpr39 缺陷小鼠的骨组成和完整性受到干扰,成骨细胞功能紊乱。
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Interdependence of free zinc changes and protein complex assembly - insights into zinc signal regulation.
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