A Cytosolic Amphiphilic α-Helix Controls the Activity of the Bile Acid-sensitive Ion Channel (BASIC).
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.
From the Institute of Physiology, RWTH Aachen University, D-52074 Aachen, Germany and.
Axel
A
Schmidt
From the Institute of Physiology, RWTH Aachen University, D-52074 Aachen, Germany and.
Daniel
D
Löhrer
the Department of Physics and Astronomy, McMaster University, Hamilton, Ontario L8S 4M1, Canada.
Richard J
RJ
Alsop
From the Institute of Physiology, RWTH Aachen University, D-52074 Aachen, Germany and.
Pia
P
Lenzig
From the Institute of Physiology, RWTH Aachen University, D-52074 Aachen, Germany and.
Adrienne
A
Oslender-Bujotzek
From the Institute of Physiology, RWTH Aachen University, D-52074 Aachen, Germany and.
Monika
M
Wirtz
the Department of Physics and Astronomy, McMaster University, Hamilton, Ontario L8S 4M1, Canada.
Maikel C
MC
Rheinstädter
From the Institute of Physiology, RWTH Aachen University, D-52074 Aachen, Germany and.
Stefan
S
Gründer
From the Institute of Physiology, RWTH Aachen University, D-52074 Aachen, Germany and. Electronic address: dwiemuth@ukaachen.de.
Dominik
D
Wiemuth
D000818:Animals; D002462:Cell Membrane / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D003600:Cytosol / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D029363:Organic Anion Transporters, Sodium-Dependent / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000072417:Protein Domains; D017433:Protein Structure, Secondary; D051381:Rats; D027981:Symporters / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014982:Xenopus laevis
D029363:Organic Anion Transporters, Sodium-Dependent; D027981:Symporters; C071908:sodium-bile acid cotransporter
BASIC; BLINaC; Deg/ENaC; X-ray scattering; Xenopus; amphiphilic helix; bile acid; cholesterol; ion channel; patch clamp
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