Targeting Mechanisms of High Voltage-Activated Ca²⁺ Channels

Functional voltage-dependent Ca²⁺ channel complexes are assembled by three to four subunits: α₁, β, α ₂δ subunits (C. Leveque et al., 1994, J. Biol Chem. 269, 6306-6312; M. W. McEnery et al., 1991, Proc. Natl. Acad. Sci. U.S.A. 88, 11095-11099) and at least in muscle cells also γ subunits (B. M. Curtis and W. A. Catterall, 1984, Biochemistry 23, 2113-2118). Ca²⁺ channels mediate the voltage-dependent Ca²⁺ influx in subcellular compartments, triggering such diverse processes as neurotransmitter release, dendritic action potentials, excitation-contraction, and excitation-transcription coupling. The targeting of biophysically defined Ca²⁺ channel complexes to the correct subcellular structures is, thus, critical to proper cell and physiological functioning. Despite their importance, surprisingly little is known about the targeting mechanisms by which Ca²⁺ channel complexes are transported to their site of function. Here we summarize what we know about the targeting of Ca²⁺ channel complexes through the cell to the plasma membrane and subcellular structures.