Investigating sterol and redox regulation of the ion channel activity of CLIC1 using tethered bilayer membranes

Al Khamici, H; Hossain, KR; Cornell, BA; Valenzuela, SM

Investigating sterol and redox regulation of the ion channel activity of CLIC1 using tethered bilayer membranes

Al Khamici, H Hossain, KR

Cornell, BA

Valenzuela, SM

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Publication Type:: Journal Article
Citation:: Membranes, 2016, 6 (4)
Issue Date:: 2016-12-08

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Field	Value	Language
dc.contributor.author	Al Khamici, H	en_US
dc.contributor.author	Hossain, KR https://orcid.org/0000-0003-4506-1491	en_US
dc.contributor.author	Cornell, BA https://orcid.org/0000-0003-4166-3241	en_US
dc.contributor.author	Valenzuela, SM https://orcid.org/0000-0001-5934-6047	en_US
dc.date.available	2016-12-05	en_US
dc.date.issued	2016-12-08	en_US
dc.identifier.citation	Membranes, 2016, 6 (4)	en_US
dc.identifier.uri	http://hdl.handle.net/10453/116803
dc.description.abstract	© 2016 by the authors; licensee MDPI, Basel, Switzerland. The Chloride Intracellular Ion Channel (CLIC) family consists of six conserved proteins in humans. These are a group of enigmatic proteins, which adopt both a soluble and membrane bound form. CLIC1 was found to be a metamorphic protein, where under specific environmental triggers it adopts more than one stable reversible soluble structural conformation. CLIC1 was found to spontaneously insert into cell membranes and form chloride ion channels. However, factors that control the structural transition of CLIC1 from being an aqueous soluble protein into a membrane bound protein have yet to be adequately described. Using tethered bilayer lipid membranes and electrical impedance spectroscopy system, herein we demonstrate that CLIC1 ion channel activity is dependent on the type and concentration of sterols in bilayer membranes. These findings suggest that membrane sterols play an essential role in CLIC1’s acrobatic switching from a globular soluble form to an integral membrane form, promoting greater ion channel conductance in membranes. What remains unclear is the precise nature of this regulation involving membrane sterols and ultimately determining CLIC1’s membrane structure and function as an ion channel. Furthermore, our impedance spectroscopy results obtained using CLIC1 mutants, suggest that the residue Cys24 is not essential for CLIC1’s ion channel function. However Cys24 does appear important for optimal ion channel activity. We also observe differences in conductance between CLIC1 reduced and oxidized forms when added to our tethered membranes. Therefore, we conclude that both membrane sterols and redox play a role in the ion channel activity of CLIC1.	en_US
dc.relation.ispartof	Membranes	en_US
dc.relation.isbasedon	10.3390/membranes6040051	en_US
dc.title	Investigating sterol and redox regulation of the ion channel activity of CLIC1 using tethered bilayer membranes	en_US
dc.type	Journal Article
utslib.citation.volume	4	en_US
utslib.citation.volume	6	en_US
utslib.for	1101 Medical Biochemistry and Metabolomics	en_US
utslib.for	0904 Chemical Engineering	en_US
utslib.for	0905 Civil Engineering	en_US
utslib.for	0907 Environmental Engineering	en_US
pubs.embargo.period	Not known	en_US
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Life Sciences
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Mathematical and Physical Sciences
pubs.organisational-group	/University of Technology Sydney/Strength - CHT - Health Technologies
utslib.copyright.status	open_access
pubs.issue	4	en_US
pubs.publication-status	Published	en_US
pubs.volume	6	en_US

Abstract:

© 2016 by the authors; licensee MDPI, Basel, Switzerland. The Chloride Intracellular Ion Channel (CLIC) family consists of six conserved proteins in humans. These are a group of enigmatic proteins, which adopt both a soluble and membrane bound form. CLIC1 was found to be a metamorphic protein, where under specific environmental triggers it adopts more than one stable reversible soluble structural conformation. CLIC1 was found to spontaneously insert into cell membranes and form chloride ion channels. However, factors that control the structural transition of CLIC1 from being an aqueous soluble protein into a membrane bound protein have yet to be adequately described. Using tethered bilayer lipid membranes and electrical impedance spectroscopy system, herein we demonstrate that CLIC1 ion channel activity is dependent on the type and concentration of sterols in bilayer membranes. These findings suggest that membrane sterols play an essential role in CLIC1’s acrobatic switching from a globular soluble form to an integral membrane form, promoting greater ion channel conductance in membranes. What remains unclear is the precise nature of this regulation involving membrane sterols and ultimately determining CLIC1’s membrane structure and function as an ion channel. Furthermore, our impedance spectroscopy results obtained using CLIC1 mutants, suggest that the residue Cys24 is not essential for CLIC1’s ion channel function. However Cys24 does appear important for optimal ion channel activity. We also observe differences in conductance between CLIC1 reduced and oxidized forms when added to our tethered membranes. Therefore, we conclude that both membrane sterols and redox play a role in the ion channel activity of CLIC1.

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http://hdl.handle.net/10453/116803