Anoctamin 9/TMEM16J is a cation channel activated by cAMP/PKA signal
Anoctamin 9/TMEM16J is a cation channel activated by cAMP/PKA signal
复制标题
DOI：
10.1016/j.ceca.2017.12.003
复制
发表时间：
2018-05-01
期刊：
影响因子：
4
通讯作者：
Oh, Uhtaek
中科院分区：
文献类型：
--
作者：
Kim, Hyungsup;Kim, Hyesu;Oh, Uhtaek
Anoctamins（ANO）是由10个同源物组成的多功能膜蛋白。ANO 1（TMEM 16 A）和ANO 2（TMEM 16 B）是由细胞内钙激活的阴离子通道，其调节许多生理功能。ANO 6是一种在细胞膜上重新分配磷脂的乱序酶。其他同系物的特征还不清楚。我们发现ANO 9/TMEM 16 J是一个由cAMP依赖性蛋白激酶A（PKA）激活的阳离子通道。在表达ANO 9的全细胞中，细胞内cAMP激活的强电流可被PKA阻断剂抑制。霍乱毒素，持续刺激腺苷酸环化酶激活ANO 9的PKA的应用。cAMP诱导的ANO 9电流对阳离子是可渗透的。cAMP依赖性的ANO 9电流被细胞内Ca-2+增强。Ano 9转录本在肠道中占主导地位。人肠SW 480细胞表达高水平的Ano 9转录本，并显示PKA通道可逆cAMP依赖性电流。我们得出的结论是，ANO 9是一种由cAMP/PKA途径激活的阳离子通道，可能在肠道功能中发挥作用。
Anoctamins (ANOs) are multifunctional membrane proteins that consist of 10 homologs. ANO1 (TMEM16A) and ANO2 (TMEM16B) are anion channels activated by intracellular calcium that meditate numerous physiological functions. ANO6 is a scramblase that redistributes phospholipids across the cell membrane. The other homologs are not well characterized. We found ANO9/TMEM16J is a cation channel activated by a cAMP-dependent protein kinase A (PKA). Intracellular cAMP-activated robust currents in whole cells expressing ANO9, which were inhibited by a PKA blocker. A cholera toxin that persistently stimulated adenylate cyclase activated ANO9 as did the application of PKA. The cAMP-induced ANO9 currents were permeable to cations. The cAMP-dependent ANO9 currents were augmented by intracellular Ca-2+. Ano9 transcripts were predominant in the intestines. Human intestinal SW480 cells expressed high levels of Ano9 transcripts and showed PKA inhibitor-reversible cAMP-dependent currents. We conclude that ANO9 is a cation channel activated by a cAMP/PKA pathway and could play a role in intestine function.