The I-II loop of the Ca2+ channel alpha1 subunit contains an endoplasmic reticulum retention signal antagonized by the beta subunit

Neuron. 2000 Jan;25(1):177-90. doi: 10.1016/s0896-6273(00)80881-8.


The auxiliary beta subunit is essential for functional expression of high voltage-activated Ca2+ channels. This effect is partly mediated by a facilitation of the intracellular trafficking of alpha1 subunit toward the plasma membrane. Here, we demonstrate that the I-II loop of the alpha1 subunit contains an endoplasmic reticulum (ER) retention signal that severely restricts the plasma membrane incorporation of alpha1 subunit. Coimmunolabeling reveals that the I-II loop restricts expression of a chimera CD8-I-II protein to the ER. The beta subunit reverses the inhibition imposed by the retention signal. Extensive deletion of this retention signal in full-length alpha1 subunit facilitates the cell surface expression of the channel in the absence of beta subunit. Our data suggest that the beta subunit favors Ca2+ channel plasma membrane expression by inhibiting an expression brake contained in beta-binding alpha1 sequences.

MeSH terms

  • Animals
  • Biological Transport / genetics
  • COS Cells
  • Calcium Channels / chemistry*
  • Calcium Channels / genetics*
  • Calcium Channels / metabolism
  • Cell Membrane / chemistry*
  • Cell Membrane / metabolism
  • Cytoplasm / chemistry
  • Endoplasmic Reticulum / chemistry*
  • Endoplasmic Reticulum / metabolism
  • Gene Deletion
  • Gene Expression / physiology
  • Ion Channel Gating / physiology*
  • Membrane Potentials / drug effects
  • Membrane Potentials / physiology
  • Mutagenesis / physiology
  • Oocytes / physiology
  • Potassium / pharmacology
  • Protein Structure, Tertiary
  • Rabbits
  • Recombinant Fusion Proteins / analysis
  • Recombinant Fusion Proteins / physiology
  • Up-Regulation / genetics
  • Xenopus laevis


  • Calcium Channels
  • Recombinant Fusion Proteins
  • Potassium