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C-terminal Fragments of the Alpha 1C (CaV1.2) Subunit Associate With and Regulate L-type Calcium Channels Containing C-terminal-truncated Alpha 1C Subunits

C-terminal Fragments of the Alpha 1C (CaV1.2) Subunit Associate With and Regulate L-type Calcium Channels Containing C-terminal-truncated Alpha 1C Subunits

T Gao, A E Cuadra, H Ma, M Bunemann, B L Gerhardstein, T Cheng, R T Eick, M M Hosey

J Biol Chem. 2001 Jun 15;276(24):21089-97.

PMID: 11274161

Abstract:

L-type Ca(2+) channels in native tissues have been found to contain a pore-forming alpha(1) 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 alpha(1C) (Ca(V)1.2) subunits, we performed electrophysiological and biochemical experiments. In tsA201 cells expressing either wild type or C-terminal-truncated alpha(1C) subunits in combination with a beta(2a) subunit, truncation of the alpha(1C) 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 alpha(1C) subunits. Dialysis of cells expressing the truncated alpha(1C) subunits with C-terminal fragments applied through the patch pipette reconstituted the inhibition of the channels seen with full-length alpha(1C) 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 alpha(1C) subunits. In addition, glutathione S-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 alpha(1C) subunit can associate with C-terminal-truncated alpha(1C) subunits and inhibit the currents through L-type Ca(2+) channels.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
IAR42414012	Anti-Coronin-1C (C-terminal)			Price

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