The I-II loop of the Ca2+ channel alpha1 subunit contains an endoplasmic reticulum retention signal antagonized by the beta subunit.
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.
Bichet
D
D
Institut National de la Santé et de la Recherche Médicale U464, Faculté de Médecine Nord, Marseille, France.
Cornet
V
V
Geib
S
S
Carlier
E
E
Volsen
S
S
Hoshi
T
T
Mori
Y
Y
De Waard
M
M
D000818:Animals; D001692:Biological Transport / Q000235:genetics; D019556:COS Cells; D015220:Calcium Channels / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D002462:Cell Membrane / Q000737:chemistry* / Q000378:metabolism; D003593:Cytoplasm / Q000737:chemistry; D004721:Endoplasmic Reticulum / Q000737:chemistry* / Q000378:metabolism; D017353:Gene Deletion; D015870:Gene Expression / Q000502:physiology; D015640:Ion Channel Gating / Q000502:physiology*; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D016296:Mutagenesis / Q000502:physiology; D009865:Oocytes / Q000502:physiology; D011188:Potassium / Q000494:pharmacology; D017434:Protein Structure, Tertiary; D011817:Rabbits; D011993:Recombinant Fusion Proteins / Q000032:analysis / Q000502:physiology; D015854:Up-Regulation / Q000235:genetics; D014982:Xenopus laevis
D015220:Calcium Channels; D011993:Recombinant Fusion Proteins; D011188:Potassium