Functional characterization of homo- and heteromeric channel kinases TRPM6 and TRPM7.
Functional characterization of homo- and heteromeric channel kinases TRPM6 and TRPM7.
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DOI：
10.1085/jgp.200609502
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发表时间：
2006-05
影响因子：
3.8
通讯作者：
Yue, Lixia
中科院分区：
文献类型：
--
作者：
Li, Mingjiang;Jiang, Jianmin;Yue, Lixia
TRPM6和TRPM7是两种已知的通道激酶，在包括Mg2+稳态在内的各种生理过程中发挥重要作用。TRPM6突变可引起遗传性低镁血症和继发性低钙血症（HSH）。然而，TRPM6是否编码功能通道仍有争议。在这里，我们展示了TRPM6的几个特征，这些特征区分了TRPM6与TRPM7和TRPM6/7通道。我们发现异源表达TRPM6而非突变体TRPM6S141L产生的功能通道具有二价阳离子渗透性和pH敏感性，与TRPM7通道和TRPM6/7复合物不同。TRPM6表现出独特的单一电导，比TRPM7和TRPM6/7大2倍和1.5倍。此外，微摩尔水平的2-氨基乙氧基二苯硼酸盐（2-APB）最大限度地增加了TRPM6，但显著抑制了TRPM7通道的活性；而毫摩尔浓度的2-APB则增强了TRPM6/7和TRPM7通道的活性。此外，Mg2+和Ca2+通过TRPM6的进入被2-APB增强了三到四倍。综上所述，这些结果表明TRPM6可以形成功能性的同质通道，也可以形成异质TRPM6/7复合物。TRPM6、TRPM7和TRPM6/7这三种通道类型的独特特性表明它们可能在体内发挥不同的作用。
TRPM6 and TRPM7 are two known channel kinases that play important roles in various physiological processes, including Mg2+ homeostasis. Mutations in TRPM6 cause hereditary hypomagnesemia and secondary hypocalcemia (HSH). However, whether TRPM6 encodes functional channels is controversial. Here we demonstrate several signature features of TRPM6 that distinguish TRPM6 from TRPM7 and TRPM6/7 channels. We show that heterologous expression of TRPM6 but not the mutant TRPM6S141L produces functional channels with divalent cation permeability profile and pH sensitivity distinctive from those of TRPM7 channels and TRPM6/7 complexes. TRPM6 exhibits unique unitary conductance that is 2- and 1.5-fold bigger than that of TRPM7 and TRPM6/7. Moreover, micromolar levels of 2-aminoethoxydiphenyl borate (2-APB) maximally increase TRPM6 but significantly inhibit TRPM7 channel activities; whereas millimolar concentrations of 2-APB potentiate TRPM6/7 and TRPM7 channel activities. Furthermore, Mg2+ and Ca2+ entry through TRPM6 is enhanced three- to fourfold by 2-APB. Collectively, these results indicate that TRPM6 forms functional homomeric channels as well as heteromeric TRPM6/7 complexes. The unique characteristics of these three channel types, TRPM6, TRPM7, and TRPM6/7, suggest that they may play different roles in vivo.