Molecular components of vertebrate Mg2+-homeostasis regulation.
Molecular components of vertebrate Mg2+-homeostasis regulation.
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DOI：
10.1684/mrh.2007.0078
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发表时间：
2007-03
影响因子：
3.2
通讯作者：
C. Schmitz;Francina Deason;A. Perraud
中科院分区：
文献类型：
--
作者：
C. Schmitz;Francina Deason;A. Perraud
在过去的几十年中，Mg 2+的临床相关性和生物学意义已被充分记录。虽然多种镁离子转运途径已被生物病理学的特点，在脊椎动物中的镁离子稳态调节的假设组件的分子身份仍然不确定。遗传学、基因组学和蛋白质组学领域的最新进展以及cDNA微阵列等新技术使这一领域取得了实质性进展。线粒体Mrs 2蛋白是第一个人类Mg 2+转运蛋白，其特征在于，和一个重要的元素，为未来的分析线粒体在管理细胞内Mg 2+的作用。几个分子与镁离子转运能力已确定通过筛选，旨在寻找基因上调低镁条件下。这包括SLC 41 A1和2，ACDP 2和MagT 1。最后，阐明了导致低镁血症的两种不同遗传性疾病的分子原因，导致了claudin 16（paracellin-1）和TRPM 6的克隆和表征。尽管claudin 16在细胞旁Mg 2+转运中起关键作用，但TRPM 6参与跨细胞途径。TRPM 6和它最近的亲戚TRPM 7都是令人困惑的离子通道激酶融合，也许是最意想不到的新发现的球员在脊椎动物中的Mg 2 +-稳态的调节。
Over the past decades, the clinical relevance and biological significance of Mg2+ have been thoroughly documented. Although multiple Mg2+-transport pathways have been biophysically characterized, the molecular identity of the postulated components of Mg2+-homeostasis regulation in vertebrates remain undefined. Recent advances in the fields of genetics, genomics and proteomics, and novel technologies such as cDNA microarrays have allowed for substantial progress in this area. The mitochondrial Mrs2 protein was the first human Mg2+ transporter characterized as such, and an important element for future analyses of the role of mitochondria in managing intracellular Mg2+. Several molecules with Mg2+ transport capabilities have been identified through a screen designed to find genes upregulated under hypomagnesic conditions. This includes SLC41A1 and 2, ACDP2 and MagT1. Finally, the elucidation of the molecular cause underlying two different hereditary diseases leading to hypomagnesemia resulted in the cloning and characterization of claudin 16 (paracellin-1), and TRPM6. Whereas claudin 16 plays a crucial role in paracellular Mg2+ transport, TRPM6 is involved in the transcellular pathway. TRPM6 and its closest relative TRPM7 are both puzzling ion channel-kinase fusions, and perhaps the most unexpected newly identified players in the regulation of Mg2+-homeostasis in vertebrates.