title: Regulation of the membrane insertion and conductance activity of the metamorphic chloride intracellular channel protein CLIC1 by cholesterol.
abstract: The Chloride Intracellular ion channel protein CLIC1 has the ability to spontaneously insert into lipid membranes from a soluble, globular state. The precise mechanism of how this occurs and what regulates this insertion is still largely unknown, although factors such as pH and redox environment are known contributors. In the current study, we demonstrate that the presence and concentration of cholesterol in the membrane regulates the spontaneous insertion of CLIC1 into the membrane as well as its ion channel activity. The study employed pressure versus area change measurements of Langmuir lipid monolayer films; and impedance spectroscopy measurements using tethered bilayer membranes to monitor membrane conductance during and following the addition of CLIC1 protein. The observed cholesterol dependent behaviour of CLIC1 is highly reminiscent of the cholesterol-dependent-cytolysin family of bacterial pore-forming proteins, suggesting common regulatory mechanisms for spontaneous protein insertion into the membrane bilayer.
authors: School of Medical and Molecular Biosciences, University of Technology Sydney, Sydney, New South Wales, Australia. Stella.Valenzuela@uts.edu.au
authors: Stella M
authors: SM
authors: Valenzuela
authors: Heba
authors: H
authors: Alkhamici
authors: Louise J
authors: LJ
authors: Brown
authors: Oscar C
authors: OC
authors: Almond
authors: Sophia C
authors: SC
authors: Goodchild
authors: Sonia
authors: S
authors: Carne
authors: Paul M G
authors: PM
authors: Curmi
authors: Stephen A
authors: SA
authors: Holt
authors: Bruce A
authors: BA
authors: Cornell
mesh_terms: D001427:Bacterial Toxins / Q000378:metabolism; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism*; D018118:Chloride Channels / Q000378:metabolism* / Q000494:pharmacology; D002784:Cholesterol / Q000378:metabolism*; D006360:Heat-Shock Proteins / Q000378:metabolism; D006460:Hemolysin Proteins / Q000378:metabolism; D006801:Humans; D008051:Lipid Bilayers / Q000378:metabolism
chemical_list: D001427:Bacterial Toxins; C501966:CLIC1 protein, human; D018118:Chloride Channels; D006360:Heat-Shock Proteins; D006460:Hemolysin Proteins; D008051:Lipid Bilayers; D002784:Cholesterol; C038705:hlyA protein, Listeria monocytogenes