Ca-V Beta Controls The Endocytic Turnover Of Ca(V)1.2 L-Type Calcium Channel

Membrane depolarization activates the multisubunit Ca(V)1.2 L-type calcium channel initiating various excitation coupling responses. Intracellular trafficking into and out of the plasma membrane regulates the channel's surface expression and stability, and thus, the strength of Ca(V)1.2-mediated Ca2+ signals. The mechanisms regulating the residency time of the channel at the cell membrane are unclear. Here, we coexpressed the channel core complex Ca(V)1.2 alpha(1) pore-forming and auxiliary Ca-V beta subunits and analyzed their trafficking dynamics from single-particle-tracking trajectories. Speed histograms obtained for each subunit were best fitted to a sum of diffusive and directed motion terms. The same mean speed for the highest-mobility state underlying directed motion was found for all subunits. The frequency of this component increased by covalent linkage of Ca-V beta to Ca(V)1.2 alpha(1) suggesting that high-speed transport occurs in association with Ca-V beta. Selective tracking of Ca(V)1.2 alpha(1) along the postendocytic pathway failed to show the highly mobile state, implying Ca-V beta-independent retrograde transport. Retrograde speeds of Ca(V)1.2 alpha(1) are compatible with myosin VI-mediated backward transport. Moreover, residency time at the cell surface was significantly prolonged when Ca(V)1.2 alpha(1) was covalently linked to Ca-V beta. Thus, Ca-V beta promotes fast transport speed along anterograde trafficking and acts as a molecular switch controlling the endocytic turnover of L-type calcium channels.