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 - PubMed (original) (raw)
. 2001 Jun 15;276(24):21089-97.
doi: 10.1074/jbc.M008000200. Epub 2001 Mar 26.
Affiliations
- PMID: 11274161
- DOI: 10.1074/jbc.M008000200
Free article
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 et al. J Biol Chem. 2001.
Free article
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.
Similar articles
- Role of the C terminus of the alpha 1C (CaV1.2) subunit in membrane targeting of cardiac L-type calcium channels.
Gao T, Bunemann M, Gerhardstein BL, Ma H, Hosey MM. Gao T, et al. J Biol Chem. 2000 Aug 18;275(33):25436-44. doi: 10.1074/jbc.M003465200. J Biol Chem. 2000. PMID: 10816591 - A sequence in the carboxy-terminus of the alpha(1C) subunit important for targeting, conductance and open probability of L-type Ca(2+) channels.
Kepplinger KJ, Kahr H, Förstner G, Sonnleitner M, Schindler H, Schmidt T, Groschner K, Soldatov NM, Romanin C. Kepplinger KJ, et al. FEBS Lett. 2000 Jul 21;477(3):161-9. doi: 10.1016/s0014-5793(00)01791-9. FEBS Lett. 2000. PMID: 10908714 - Proteolytic processing of the C terminus of the alpha(1C) subunit of L-type calcium channels and the role of a proline-rich domain in membrane tethering of proteolytic fragments.
Gerhardstein BL, Gao T, Bünemann M, Puri TS, Adair A, Ma H, Hosey MM. Gerhardstein BL, et al. J Biol Chem. 2000 Mar 24;275(12):8556-63. doi: 10.1074/jbc.275.12.8556. J Biol Chem. 2000. PMID: 10722694 - Regulation of Cav1.2 current: interaction with intracellular molecules.
Kobayashi T, Yamada Y, Fukao M, Tsutsuura M, Tohse N. Kobayashi T, et al. J Pharmacol Sci. 2007 Apr;103(4):347-53. doi: 10.1254/jphs.cr0070012. Epub 2007 Apr 4. J Pharmacol Sci. 2007. PMID: 17409629 Review. - Regulation of voltage-gated calcium channels by proteolysis.
Abele K, Yang J. Abele K, et al. Sheng Li Xue Bao. 2012 Oct 25;64(5):504-14. Sheng Li Xue Bao. 2012. PMID: 23090491 Free PMC article. Review.
Cited by
- Convergent regulation of CaV1.2 channels by direct phosphorylation and by the small GTPase RAD in the cardiac fight-or-flight response.
Hovey L, Gamal El-Din TM, Catterall WA. Hovey L, et al. Proc Natl Acad Sci U S A. 2022 Oct 18;119(42):e2208533119. doi: 10.1073/pnas.2208533119. Epub 2022 Oct 10. Proc Natl Acad Sci U S A. 2022. PMID: 36215501 Free PMC article. - Regulation of Cardiac Calcium Channels in the Fight-or-Flight Response.
Catterall WA. Catterall WA. Curr Mol Pharmacol. 2015;8(1):12-21. doi: 10.2174/1874467208666150507103417. Curr Mol Pharmacol. 2015. PMID: 25966697 Free PMC article. Review. - Impairment of β-adrenergic regulation and exacerbation of pressure-induced heart failure in mice with mutations in phosphoregulatory sites in the cardiac CaV1.2 calcium channel.
Hovey L, Guo X, Chen Y, Liu Q, Catterall WA. Hovey L, et al. Front Physiol. 2023 Feb 8;14:1049611. doi: 10.3389/fphys.2023.1049611. eCollection 2023. Front Physiol. 2023. PMID: 36846334 Free PMC article. - Facilitation of L-type Ca2+ channels in dendritic spines by activation of beta2 adrenergic receptors.
Hoogland TM, Saggau P. Hoogland TM, et al. J Neurosci. 2004 Sep 29;24(39):8416-27. doi: 10.1523/JNEUROSCI.1677-04.2004. J Neurosci. 2004. PMID: 15456814 Free PMC article. - CaMKII tethers to L-type Ca2+ channels, establishing a local and dedicated integrator of Ca2+ signals for facilitation.
Hudmon A, Schulman H, Kim J, Maltez JM, Tsien RW, Pitt GS. Hudmon A, et al. J Cell Biol. 2005 Nov 7;171(3):537-47. doi: 10.1083/jcb.200505155. J Cell Biol. 2005. PMID: 16275756 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Miscellaneous