ANOs 3-7 in the anoctamin/Tmem16 Cl- channel family are intracellular proteins
ANOs 3-7 in the anoctamin/Tmem16 Cl- channel family are intracellular proteins
复制标题
anoctamin/tmem16 Cl-通道家族中的 ANO 3-7 是细胞内蛋白
DOI：
10.1152/ajpcell.00140.2011
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发表时间：
2012-02-01
影响因子：
5.5
通讯作者：
Hartzell, H. Criss
中科院分区：
文献类型：
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作者：
Duran, Charity;Qu, Zhiqiang;Hartzell, H. Criss
杜兰C，曲Z，Osunkoya AO，崔Y，Hartzell HC。Anoctamin/Tmem 16 Cl-通道家族中的ANO 3-7是细胞内蛋白。Am J Physiol Cell Physiol 302：C482-C493，2012.首次发表于2011年11月9日; doi：10.1152/ajpcell.00140.2011.Ca2+激活的Cl-通道（CaCC）参与许多生理功能，如神经元兴奋性、感觉转导和跨上皮液体运输。最近，研究表明异源表达的anoctamins ANO 1和ANO 2产生类似于天然CaCC的电流。Anoctamin家族（也称为Tmem 16）由10个成员组成，但不知道该家族的所有成员是否都是CaCC。HEK 293细胞中ANO 3-7的表达不产生由细胞内Ca 2+激活的Cl-电流，如通过全细胞膜片钳电生理学所测定的。随着共聚焦成像的使用，当异源表达时，只有ANO 1和ANO 2进入质膜。此外，人前列腺中内源性表达的ANO 7主要是细胞内的。我们采用嵌合的方法来识别对通道运输和功能至关重要的区域。然而，我们制造的ANO 1和ANO 5/7的嵌合体都没有运输到质膜。我们的研究结果表明，细胞内anoctamins可能是内质网蛋白，虽然它仍然是未知的，这些家庭成员是否CaCC。确定anoctamin家族成员在离子转运中的作用对于理解它们在生理学和疾病中的功能至关重要。
Duran C, Qu Z, Osunkoya AO, Cui Y, Hartzell HC. ANOs 3-7 in the anoctamin/Tmem16 Cl- channel family are intracellular proteins. Am J Physiol Cell Physiol 302: C482-C493, 2012. First published November 9, 2011; doi: 10.1152/ajpcell.00140.2011.Ca2+-activated Cl- channels (CaCCs) participate in numerous physiological functions such as neuronal excitability, sensory transduction, and transepithelial fluid transport. Recently, it was shown that heterologously expressed anoctamins ANO1 and ANO2 generate currents that resemble native CaCCs. The anoctamin family (also called Tmem16) consists of 10 members, but it is not known whether all members of the family are CaCCs. Expression of ANOs 3-7 in HEK293 cells did not generate Cl- currents activated by intracellular Ca2+, as determined by whole cell patch clamp electrophysiology. With the use of confocal imaging, only ANO1 and ANO2 traffic to the plasma membrane when expressed heterologously. Furthermore, endogenously expressed ANO7 in the human prostate is predominantly intracellular. We took a chimeric approach to identify regions critical for channel trafficking and function. However, none of the chimeras of ANO1 and ANO5/7 that we made trafficked to the plasma membrane. Our results suggest that intracellular anoctamins may be endoplasmic reticulum proteins, although it remains unknown whether these family members are CaCCs. Determining the role of anoctamin family members in ion transport will be critical to understanding their functions in physiology and disease.