CLIC-2 modulates cardiac ryanodine receptor Ca2+ release channels

Philip G. Board*, Marjorie Coggan, Sarah Watson, Peter W. Gage, Angela F. Dulhunty

*Corresponding author for this work

    Research output: Contribution to journalArticlepeer-review

    70 Citations (Scopus)

    Abstract

    We have examined the biochemical and functional properties of the recently identified, uncharacterised CLIC-2 protein. Sequence alignments showed that CLIC-2 has a high degree of sequence similarity with CLIC-1 and some similarity to the omega class of glutathione transferases (GSTO). A homology model of CLIC-2 based on the crystal structure of CLIC-1 suggests that CLIC-2 belongs to the GST structural family but, unlike the GSTs, CLIC-2 exists as a monomer. It also has an unusual enzyme activity profile. While the CXXC active site motif is conserved between CLIC-2 and the glutaredoxins, no thiol transferase activity was detected. In contrast, low glutathione peroxidase activity was recorded. CLIC-2 was found to be widely distributed in tissues including heart and skeletal muscle. Functional studies showed that CLIC-2 inhibited cardiac ryanodine receptor Ca2+ release channels in lipid bilayers when added to the cytoplasmic side of the channels and inhibited Ca2+ release from cardiac sarcoplasmic reticulum vesicles. The inhibition of RyR channels was reversed by removing CLIC-2 from the solution or by adding an anti-CLIC-2 antibody. The results suggest that one function of CLIC-2 might be to limit Ca2+ release from internal stores in cells.

    Original languageEnglish
    Pages (from-to)1599-1612
    Number of pages14
    JournalInternational Journal of Biochemistry and Cell Biology
    Volume36
    Issue number8
    DOIs
    Publication statusPublished - Aug 2004

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