Voltage-gated calcium channel α2δ subunits: an assessment of proposed novel roles

Voltage-gated calcium (Ca V ) channels are associated with β and α 2 δ auxiliary subunits. This review will concentrate on the function of the α 2 δ protein family, which has four members. The canonical role for α 2 δ subunits is to convey a variety of properties on the Ca V 1 and Ca V 2 channels, increasing the density of these channels in the plasma membrane and also enhancing their function. More recently, a diverse spectrum of non-canonical interactions for α 2 δ proteins has been proposed, some of which involve competition with calcium channels for α 2 δ or increase α 2 δ trafficking and others which mediate roles completely unrelated to their calcium channel function. The novel roles for α 2 δ proteins which will be discussed here include association with low-density lipoprotein receptor-related protein 1 (LRP1), thrombospondins, α-neurexins, prion proteins, large conductance (big) potassium (BK) channels, and N -methyl-d-aspartate (NMDA) receptors.