Schmidt Axel, Löhrer Daniel, Alsop Richard J, Lenzig Pia, Oslender-Bujotzek Adrienne, Wirtz Monika, Rheinstädter Maikel C, Gründer Stefan, Wiemuth Dominik
From the Institute of Physiology, RWTH Aachen University, D-52074 Aachen, Germany and.
the Department of Physics and Astronomy, McMaster University, Hamilton, Ontario L8S 4M1, Canada.
J Biol Chem. 2016 Nov 18;291(47):24551-24565. doi: 10.1074/jbc.M116.756437. Epub 2016 Sep 27.
The bile acid-sensitive ion channel (BASIC) is a member of the degenerin/epithelial Na channel (Deg/ENaC) family of ion channels. It is mainly found in bile duct epithelial cells, the intestinal tract, and the cerebellum and is activated by alterations of its membrane environment. Bile acids, one class of putative physiological activators, exert their effect by changing membrane properties, leading to an opening of the channel. The physiological function of BASIC, however, is unknown. Deg/ENaC channels are characterized by a trimeric subunit composition. Each subunit is composed of two transmembrane segments, which are linked by a large extracellular domain. The termini of the channels protrude into the cytosol. Many Deg/ENaC channels contain regulatory domains and sequence motifs within their cytosolic domains. In this study, we show that BASIC contains an amphiphilic α-helical structure within its N-terminal domain. This α-helix binds to the cytosolic face of the plasma membrane and stabilizes a closed state. Truncation of this domain renders the channel hyperactive. Collectively, we identify a cytoplasmic domain, unique to BASIC, that controls channel activity via membrane interaction.
胆汁酸敏感离子通道（BASIC）是退化素/上皮钠通道（Deg/ENaC）家族离子通道的成员。它主要存在于胆管上皮细胞、肠道和小脑中，并通过其膜环境的改变而被激活。胆汁酸是一类假定的生理激活剂，通过改变膜特性发挥作用，导致通道开放。然而，BASIC的生理功能尚不清楚。Deg/ENaC通道的特征是三聚体亚基组成。每个亚基由两个跨膜片段组成，这两个片段由一个大的细胞外结构域连接。通道的末端伸向细胞质。许多Deg/ENaC通道在其细胞质结构域内包含调节结构域和序列基序。在本研究中，我们表明BASIC在其N端结构域内包含一个两亲性α螺旋结构。这个α螺旋与质膜的细胞质面结合并稳定关闭状态。该结构域的截断使通道过度活跃。总体而言，我们鉴定出一个BASIC特有的细胞质结构域，它通过膜相互作用控制通道活性。
