On the targeting of voltage-gated calcium channels to neurotransmitter release sites

At the presynaptic active zone, voltage-gated Ca²⁺ channels (Ca_Vs) mediate Ca²⁺ entry for neurotransmitter release. Ca_Vs are a large family of proteins, and different subtypes have distinct localizations across neuronal somata, dendrites and axons. Here, we review how neurons establish and maintain a specific Ca_V repertoire at their active zones. We focus on molecular determinants for cargo assembly, presynaptic delivery and release site tethering, and we discuss recent work that has identified key roles of the Ca_V intracellular C-terminus. Finally, we evaluate how these mechanisms may differ between different types of neurons. Work on Ca_Vs provides insight into the protein targeting pathways that help maintain neuronal polarity.