C-terminal Fragments of the α1C(CaV1.2) Subunit Associate with and Regulate L-type Calcium Channels Containing C-terminal-truncated α1CSubunits*
By T. Gao, A. Cuadra, Hong Ma, M. Bünemann, B. Gerhardstein, T. Cheng, R. T. Eick, M. Hosey. Journal of Biological Chemistry, 2001
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L-type Ca2+ channels in native tissues have been found to contain a pore-forming α1 subunit that is often truncated at the C terminus. However, the C terminus contains many important domains that regulate channel function. To test the hypothesis that C-terminal fragments may associate with and regulate C-terminal-truncated α1C(CaV1.2) subunits, we performed electrophysiological and biochemical experiments. In tsA201 cells expressing either wild type or C-terminal-truncated α1C subunits in combination with a β2a subunit, truncation of the α1C subunit by as little as 147 amino acids led to a 10–15-fold increase in currents compared with those obtained from control, full-length α1C subunits. Dialysis of cells expressing the truncated α1C subunits with C-terminal fragments applied through the patch pipette reconstituted the inhibition of the channels seen with full-length α1C subunits. In addition, C-terminal deletion mutants containing a tethered C terminus also exhibited the C-terminal-induced inhibition. Immunoprecipitation assays demonstrated the association of the C-terminal fragments with truncated α1C subunits. In addition, glutathioneS-transferase pull-down assays demonstrated that the C-terminal inhibitory fragment could associate with at least two domains within the C terminus. The results support the hypothesis the C- terminal fragments of the α1C subunit can associate with C-terminal-truncated α1C subunits and inhibit the currents through L-type Ca2+ channels.
Subfields: Cardiology and Cardiovascular Medicine, Cellular and Molecular Neuroscience, Molecular Biology
View Paper: https://www.semanticscholar.org/paper/85a81df9f5a8fd3e0a2e1a66971a990f52903b30
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Citations in the corpus
- Voltage-gated calcium channels. (2011, background): “2 channels in vitro (Gerhardstein et al. 2000; Gao et al. 2001; Hulme et al. 2005) and in transfected cells (Hulme et al.”