Complexes of the α(1C) and β subunits generate the necessary signal for membrane targeting of class C L-type calcium channels

Tianyan Gao, Andy J. Chien, M. Marlene Hosey

Research output: Contribution to journalArticlepeer-review

111 Scopus citations

Abstract

In the present study, we investigated the role of channel subunits in the membrane targeting of voltage-dependent L-type calcium channel complexes. We co-expressed the calcium channel pore-forming α(1C) subunit with different accessory β subunits in HEK-tsA201 cells and examined the subcellular localization of the channel subunits by immunohistochemistry using confocal microscopy and whole-cell radioligand binding studies. While the pore-forming α(1C) subunit exhibited perinuclear staining when expressed alone, and several of the wild-type and mutant β subunits also exhibited intracellular staining, co-expression of the α(1C) subunit with either the wild-type β(2a) subunit, a palmitoylation-deficient β(2a)(C3S/C4S) mutant or three other nonpalmitoylated β isoforms (β(1b),β3, and β4 subunits) resulted in the redistribution of both the α(1C) and β subunits into clusters along the cell surface. Furthermore, the redistribution of calcium channel complexes to the plasma membrane was observed when α(1C) was co- expressed with an N- and C-terminal truncated mutant β(2a) containing only the central conserved regions. However, when the α(1C) subunit was co- expressed with an α1β interaction-deficient mutant, β(2a)BID-, we did not observe formation of the channels at the plasma membrane. In addition, an Src homology 3 motif mutant of β(2a) that was unable to interact with the α(1C) subunit also failed to target channel complexes to the plasma membrane. Interestingly, co-expression of the pore-forming α(1C) subunit with the largely peripheral accessory α2δ subunit was ineffective in recruiting (α1C) to the plasma membrane, while codistribution of all three subunits was observed when β(2a) was co-expressed with the α(1C) and α2δ subunits. Taken together, our results suggested that the signal necessary for correct plasma membrane targeting of the class C L-type calcium channel complexes is generated as a result of a functional interaction between the α1 and subunits.

Original languageEnglish
Pages (from-to)2137-2144
Number of pages8
JournalJournal of Biological Chemistry
Volume274
Issue number4
DOIs
StatePublished - Jan 22 1999

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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