A Cytosolic Amphiphilic alpha-Helix Controls the Activity of the Bile Acid-sensitive Ion Channel (BASIC)

作者:Schmidt Axel; Lohrer Daniel; Alsop Richard J; Lenzig Pia; Oslender Bujotzek Adrienne; Wirtz Monika; Rheinstadter Maikel C; Grunder Stefan; Wiemuth Dominik*
来源:JOURNAL OF BIOLOGICAL CHEMISTRY, 2016, 291(47): 24551-24565.
DOI:10.1074/jbc.M116.756437

摘要

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 alpha-helical structure within its N-terminal domain. This alpha-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.

  • 出版日期2016-11-18