Molecular architecture of Ca²⁺ channel complexes organized by Ca_Vβ subunits in presynaptic active zones

Fine regulation of neurotransmitter release at presynaptic active zones is crucial for nervous system adaptive functions, including learning, memory and cognition. Neurotransmitter release is controlled by Ca²⁺ influx into the presynaptic active zones via voltage-gated Ca²⁺ channels (VGCCs). Therefore, the molecular organization of VGCC complexes at the active zones is important for Ca²⁺-triggered neurotransmitter release. Through rigorous investigation about VGCC complexes at active zones, it is becoming clear that active zone proteins impact functionally on VGCCs through direct or indirect interaction with Ca_Vα₁ and/or Ca_Vβ subunits. Specifically, Rab3-interacting molecules (RIMs), which modulate the small G protein Rab3 that is involved in synaptic vesicle trafficking, have been identified in VGCC complexes. In this review, we mainly discuss active zone proteins that form complexes with VGCCs through Ca_Vβ subunits and how these proteins regulate the function of VGCCs in neurotransmitter release.