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bioRxiv · 10.1101/2021.03.25.437080

α2δ-2 is Required for Functional Postsynaptic Calcium Channel Nanodomain Signaling

Beeson, K.·Westbrook, G.·Schnell, E.
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Abstract

2{delta} proteins (CACNA2D1-4) are required for normal neurological function, although how they control neuronal output remains unclear. Using whole-cell recordings of mouse Purkinje cells, we show 2{delta}-2 is required for functional coupling of postsynaptic voltage-dependent calcium entry with effector mechanisms controlling two different outputs, depolarization-induced suppression of excitation mediated by endocannabinoid signaling, and spike afterhyperpolarization generated by calcium-dependent potassium channels. Our findings indicate an important role for 2{delta}-2 proteins in regulating functional postsynaptic calcium channel-coupling in neurons. Significance StatementCalcium influx via membrane voltage-dependent calcium channels drives numerous neuronal processes by signaling through calcium-dependent effector molecules. Signal precision is achieved in part by calcium channel-effector coupling. In mouse Purkinje cell neurons, we show that neuronal 2{delta}-2 protein functionally couples calcium entry to two different postsynaptic calcium-dependent signals, retrograde endocannabinoid signaling and the action potential afterhyperpolarization. Our findings provide new insights about the control of calcium channel-effector coupling as well as new roles for 2{delta}-2 proteins in neurons.

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Beeson, K., Westbrook, G., Schnell, E.. 2021-03-26. α2δ-2 is Required for Functional Postsynaptic Calcium Channel Nanodomain Signaling. https://doi.org/10.1101/2021.03.25.437080

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