An active zone scaffolding protein functionally associates with presynaptic calcium channels

Abstract

The spacing between voltage-dependent calcium channels (VDCCs) and vesicles at active zones is thought to influence the dynamic properties of synaptic transmission. However, molecular determinants that maintain or regulate synaptic vesicles and VDCCs within a physiologically appropriate distance have been elusive. Here, we demonstrate a novel molecular interaction between an active zone protein and VDCCs, that controls neurotransmitter release. GST-pull down and immunoprecipitation assay showed that the active zone protein associated with VDCC β-subunits via its C-terminus. In neuroendocrine PC12 cells, acetylcholine release was significantly potentiated by the full-length, N-terminus, and C-terminus constructs, but the proportion of membrane-docked vesicles was enhanced only by the full-length. Thus, the active zone protein associated with VDCC β-subunits near the active zone supports neurotransmitter release via anchoring of neurotransmitter-containing vesicles in the vicinity of VDCCs. [J Physiol Sci. 2007;57 Suppl:S224]