CLIC1 research from Breit Group
CLIC1 is the first cloned human member of the highly conserved CLIC family of intracellular chloride ion channel proteins. Proteins of this family are unusual for ion channels: They are structurally related to the GST omega proteins, are small in size, are readily soluble and have the capacity to move on and off membranes. Whilst CLIC1 has been extensively studied and characterized electrophysiology and high-resolution structures of CLIC1 in its soluble form have been obtained, its biology is poorly understood. However, gene knockout mice have mildly impaired platelet function and its blockade limits inflammatory responses.

Current CLIC1 Research Projects

• The mechanism of action of CLIC1 in control of chronic inflammatory processes
• Structure/function of CLIC1

Selected CLIC1 Publications

• Valenzuela S, Martin DK, Warton K, Por SB, Robbins JMR, Bootcov MR, Schofield PR, Campbell TJ, Breit SN. Molecular cloning and expression of a chloride ion channel of cell nuclei. J Biol Chem. 1997; 272 : 12575-12582.
• Harrop SJ^#, DeMaere MZ^#, Fairlie WD, Reztsova T, Valenzuela SM, Mazzanti M,Tonini R, Qiu MR, Jankova L, Warton K, Bauskin AR, Wu WM, Pankhurst S, J. Campbell, Breit SN^#,  Curmi PMG^#. Crystal Structure of the Soluble Form of the Intracellular Chloride Channel NCC27 (CLIC1) at 1.4Å Resolution. J Biol Chem. 2001. 276:44993-45000.
• Kristina Warton, Raffaella Tonini, W. Douglas Fairlie, Jacqueline M Matthews, Stella M. Valenzuela,  Min Ru Qiu, Wan Man Wu, Susan Pankhurst, Asne R Bauskin, Stephen J. Harrop, Terence J. Campbell, Paul M. G. Curmi, Samuel N. Breit^#, Michele Mazzanti^#. Recombinant CLIC1 (NCC27) assembles in lipid bilayers via a pH-dependent two-state process to form chloride ion channels with identical characteristics to those observed in CHO cells expressing CLIC1. J Biol Chem 2002. 277:26003-26011.
• Dene R. Littler ^#, Stephen J. Harrop^#, W. Douglas Fairlie^#, Greg Pankhurst, Susan Pankhurst, Matthew Z. DeMaere, Wan Man Wu, Terence J. Campbell, Asne R Bauskin, Raffaella Tonini, Michele Mazzanti, Samuel N. Breit^#, Paul M.G. Curmi^#. The intracellular chloride ion channel protein CLIC1 undergoes a redox-controlled structural. J Biol Chem 2004; 279:9298-305.
• G Novarino, C Fabrizi, R Tonini, Denti MA, L Malchiodi-Albedi, GM Lauro, B Sacchetti, S Paradisi, A Ferroni, PMG Curmi SN Breit and M Mazzanti.  Involvement of the intracelIular ion channel CLIC1, in microglial-mediated b-amyloid induced toxicity. J Neurosci. 2004. 24:5322-5330.
• Rosemary H. Milton, Rosella Abeti, Stefania Averaimo, Silvia DeBiasi, Laura Vitellaro, Lele Jiang. Paul M. G. Curmi, Samuel N. Breit, Michael R. Duchen, and Michele Mazzanti. CLIC1 Function Is Required for b-Amyloid-Induced Generation of Reactive Oxygen Species by Microglia. J Neurosci. 2008.28:11488-11499.
• Goodchild SC, Howell MW, Cordina NM, Littler DR, Breit SN, Curmi PM, Brown LJ. Oxidation promotes insertion of the CLIC1 chloride intracellular channel into the membrane. Eur Biophys J. 2009:129-138.
• Qiu MR, Jiang L, Matthaei KI, Schoenwaelder SM, Kuffner T, Mangin P, Joseph JE, Low J, Connor D, Valenzuela SM, Curmi PM, Brown LJ, Mahaut-Smith M, Jackson SP, Breit SN. Generation and characterization of mice with null mutation of the chloride intracellular channel 1 gene. Genesis. 2010.48:127-136.
• Goodchild, Sophia; Howell, Michael; Littler, Dene; Mandyam, Ramya; Sale, Kenneth; Mazzanti, Michele; Breit, Samuel; Curmi, Paul; Brown, Louise. The metamorphic response of the CLIC1 chloride intracellular ion channel protein upon membrane interaction. Biochemistry 2010. 49:5278-89.

^#Contributed equally

PubMed publications for Professor Breit