Publication Date:
2012-07-28
Description:
In the nerve terminals, the active zone protein CAST/ERC2 forms a protein complex with the other active zone proteins ELKS, Bassoon, Piccolo, RIM1 and Munc13-1, and is thought to play an organizational and functional role in neurotransmitter release. However, it remains obscure how CAST/ERC2 regulates the Ca 2+ -dependent release of neurotransmitters. Here, we show an interaction of CAST with voltage-dependent Ca 2+ channels (VDCCs), which are essential for regulating neurotransmitter release triggered by depolarization-induced Ca 2+ influx at the active zone. Using a biochemical assay, we showed that CAST was coimmunoprecipitated with the VDCC β 4 -subunit from the mouse brain. A pull-down assay revealed that the VDCC β 4 -subunit interacted directly with at least the N- and C-terminal regions of CAST. The II–III linker of VDCC α 1 -subunit also interacted with C-terminal regions of CAST; however, the interaction was much weaker than that of β 4 -subunit. Furthermore, coexpression of CAST and VDCCs in baby hamster kidney cells caused a shift in the voltage dependence of activation towards the hyperpolarizing direction. Taken together, these results suggest that CAST forms a protein complex with VDCCs, which may regulate neurotransmitter release partly through modifying the opening of VDCCs at the presynaptic active zones.
Print ISSN:
0021-924X
Electronic ISSN:
1756-2651
Topics:
Biology
,
Chemistry and Pharmacology
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