CAST/ELKS Proteins Control Voltage-Gated Ca2+ Channel Density and Synaptic Release Probability at a Mammalian Central Synapse.

Cell reports 2018 Jul 10

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In the presynaptic terminal, the magnitude and location of Ca2+ entry through voltage-gated Ca2+ channels (VGCCs) regulate the efficacy of neurotransmitter release. However, how presynaptic active zone proteins control mammalian VGCC levels and organization is unclear. To address this, we deleted the CAST/ELKS protein family at the calyx of Held, a CaV2.1 channel-exclusive presynaptic terminal. We found that loss of CAST/ELKS reduces the CaV2.1 current density with concomitant reductions in CaV2.1 channel numbers and clusters. Surprisingly, deletion of CAST/ELKS increases release probability while decreasing the readily releasable pool, with no change in active zone ultrastructure. In addition, Ca2+ channel coupling is unchanged, but spontaneous release rates are elevated. Thus, our data identify distinct roles for CAST/ELKS as positive regulators of CaV2.1 channel density and suggest that they regulate release probability through a post-priming step that controls synaptic vesicle fusogenicity. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

Citation

Wei Dong, Tamara Radulovic, R Oliver Goral, Connon Thomas, Monica Suarez Montesinos, Debbie Guerrero-Given, Akari Hagiwara, Travis Putzke, Yamato Hida, Manabu Abe, Kenji Sakimura, Naomi Kamasawa, Toshihisa Ohtsuka, Samuel M Young. CAST/ELKS Proteins Control Voltage-Gated Ca2+ Channel Density and Synaptic Release Probability at a Mammalian Central Synapse. Cell reports. 2018 Jul 10;24(2):284-293.e6