CaV1.2 calcium channels: just cut out to be regulated?

Abstract

Tight regulation of calcium entry through the L-type calcium channel CaV1.2 ensures optimal excitation-response coupling. In this issue of Neuron, Michailidis et al. (2014) demonstrate that CaV1.2 activity triggers negative feedback regulation through proteolytic cleavage of the channel within the core of the pore-forming subunit.

Figure 1

Mid-body proteolytic cleavage of the basic Ca_V1.2 pore-forming unit. This Ca²⁺-dependent cleavage, here illustrated for the II-III linker (left), gives rise to fragments that can remain together in a functional state (upper right). The fragments can also dissociate and form a mosaic pattern in the surface membrane (lower right), raising questions about their possible functional significance.