Molecular characterization of a two-domain form of the neuronal voltage-gated P/Q-type calcium channel α12.1 subunit

Jyothi Arikkath, Ricardo Felix, Christopher Ahern, Chien Chang Chen, Yasuo Mori, Inseon Song, Hee Sup Shin, Roberto Coronado, Kevin P. Campbell

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

We characterized the neuronal two-domain (95kD-α12.1) form of the α12.1 subunit of the voltage-gated calcium channels using genetic and molecular analysis. The 95kD-α12.1 is absent in neuronal preparations from CACNA1A null mouse demonstrating that α12.1 and 95kD-α12.1 arise from the same gene. A recombinant two-domain form (α1AI-II) of α12.1 associates with the β subunit and is trafficked to the plasma membrane. Translocation of the α1AI-II to the plasma membrane requires association with the β subunit, since a mutation in the α1AI-II that inhibits β subunit association reduces membrane trafficking. Though the α1AI-II protein does not conduct any voltage-gated currents, we have previously shown that it generates a high density of non-linear charge movements [Ahern et al., Proc. Natl. Acad. Sci. USA 98 (2001) 6935-6940]. In this study, we demonstrate that co-expression of the α1AI-II significantly reduces the current amplitude of α12.1/β1a2δ channels, via competition for the β subunit. Taken together, our results demonstrate a dual functional role for the α1AI-II protein, both as a voltage sensor and modulator of P/Q-type currents in recombinant systems. These studies suggest an in vivo role for the 95kD-α12.1 in altering synaptic activity via protein-protein interactions and/or regulation of P/Q-type currents.

Original languageEnglish (US)
Pages (from-to)300-308
Number of pages9
JournalFEBS Letters
Volume532
Issue number3
DOIs
StatePublished - Dec 18 2002

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Keywords

  • 95kD-α2.1
  • Calcium channels
  • Episodic ataxia type 2
  • Two-domain subunit

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

Arikkath, J., Felix, R., Ahern, C., Chen, C. C., Mori, Y., Song, I., Shin, H. S., Coronado, R., & Campbell, K. P. (2002). Molecular characterization of a two-domain form of the neuronal voltage-gated P/Q-type calcium channel α12.1 subunit. FEBS Letters, 532(3), 300-308. https://doi.org/10.1016/S0014-5793(02)03693-1