Voltage-gated calcium channel α (2)δ 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.