The I-II loop of the Ca2+ channel alpha(1) subunit contains an endoplasmicreticulum retention signal antagonized by the beta subunit

The auxiliary beta subunit is essential for functional expression of high v oltage-activated Ca2+ channels. This effect is partly mediated by a facilit ation of the intracellular trafficking of alpha(1) subunit toward the plasm a membrane. Here, we demonstrate that the I-II loop of the a, subunit conta ins an endoplasmic reticulum (ER) retention signal that severely restricts the plasma membrane incorporation of alpha(1) subunit. Coimmunolabeling rev eals 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 retentio n signal. Extensive deletion of this retention signal in full-length alpha( 1) subunit facilitates the cell surface expression of the channel in the ab sence of beta subunit. Our data suggest that the beta subunit favors Ca2+ c hannel plasma membrane expression by inhibiting an expression brake contain ed in beta-binding alpha(1) sequences.