TRPM6 and TRPM7: A Mul-TRP-PLIK-cation of channel functions.
TRPM6 and TRPM7: A Mul-TRP-PLIK-cation of channel functions.
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TRPM6和TRPM7：通道函数的MUL-TRP-PLIK-cation。
DOI：
10.2174/138920111793937880
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发表时间：
2011-01-01
影响因子：
2.8
通讯作者：
Runnels LW
中科院分区：
文献类型：
--
作者：
Runnels LW
在离子通道中，TRPM6和TRPM7是独一无二的，自从发现它们是第一个拥有自己的激酶域的离子通道后，就引起了人们的极大兴趣。在确认后不久，这两种蛋白质很快就被认为与镁稳态的调节有关。然而，对它们在小鼠和斑马鱼中的生理功能的研究揭示了这些通道激酶在早期发育中的扩展作用，包括骨骼生成和黑色素孔形成、胸腺生成、细胞黏附和神经折叠关闭。此外，TRPM6基因突变构成了继发性低钙血症低镁血症的潜在遗传缺陷，继发性低钙血症是一种罕见的常染色体隐性遗传病，其特征是血清镁含量低并伴有低钙血症。另一方面，大脑中TRPM7表达的缺失被证明成功地减轻了缺血时伴随着缺氧-葡萄糖剥夺的大部分细胞破坏。这篇综述的目的是总结这些独特的通道激酶的分子遗传学、生化、电生理和药理学研究的数据。
Unique among ion channels, TRPM6 and TRPM7 garnered much interest upon their discovery as the first ion channels to possess their own kinase domain. Soon after their identification, the two proteins were quickly linked to the regulation of magnesium homeostasis. However, study of their physiological functions in mouse and zebrafish have revealed expanding roles for these channel-kinases that include skeletogenesis and melanopore formation, thymopoiesis, cell adhesion, and neural fold closure during early development. In addition, mutations in the TRPM6 gene constitute the underlying genetic defect in hypomagnesemia with secondary hypocalcemia, a rare autosomal-recessive disease characterized by low serum magnesium accompanied by hypocalcemia. Depletion of TRPM7 expression in brain, on the other hand, proved successful in mitigating much of the cellular devastation that accompanies oxygen-glucose deprivation during ischemia. The aim of this review is to summarize the data emerging from molecular genetic, biochemical, electrophysiological, and pharmacological studies of these unique channel-kinases.