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Modulation of CaV2.1 Channels by Neuronal Calcium sensor-1 Induces Short-Term Synaptic Facilitation

Modulation of CaV2.1 Channels by Neuronal Calcium sensor-1 Induces Short-Term Synaptic Facilitation

Jin Yan, Karina Leal, Venkat G Magupalli, Evanthia Nanou, Gilbert Q Martinez, Todd Scheuer, William A Catterall

Mol Cell Neurosci. 2014 Nov;63:124-31.

PMID: 25447945

Abstract:

Facilitation and inactivation of P/Q-type Ca2+ currents mediated by Ca2+/calmodulin binding to Ca(V)2.1 channels contribute to facilitation and rapid depression of synaptic transmission, respectively. Other calcium sensor proteins displace calmodulin from its binding site and differentially modulate P/Q-type Ca2 + currents, resulting in diverse patterns of short-term synaptic plasticity. Neuronal calcium sensor-1 (NCS-1, frequenin) has been shown to enhance synaptic facilitation, but the underlying mechanism is unclear. We report here that NCS-1 directly interacts with IQ-like motif and calmodulin-binding domain in the C-terminal domain of Ca(V)2.1 channel. NCS-1 reduces Ca2 +-dependent inactivation of P/Q-type Ca2+ current through interaction with the IQ-like motif and calmodulin-binding domain without affecting peak current or activation kinetics. Expression of NCS-1 in presynaptic superior cervical ganglion neurons has no effect on synaptic transmission, eliminating effects of this calcium sensor protein on endogenous N-type Ca2+ currents and the endogenous neurotransmitter release machinery. However, in superior cervical ganglion neurons expressing wild-type Ca(V)2.1 channels, co-expression of NCS-1 induces facilitation of synaptic transmission in response to paired pulses and trains of depolarizing stimuli, and this effect is lost in Ca(V)2.1 channels with mutations in the IQ-like motif and calmodulin-binding domain. These results reveal that NCS-1 directly modulates Ca(V)2.1 channels to induce short-term synaptic facilitation and further demonstrate that CaS proteins are crucial in fine-tuning short-term synaptic plasticity.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP115044694-A	Calmodulin Binding Domain - CAS 115044-69-4		115044-69-4	Price

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