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Calcium Sensors of Neurotransmitter Release

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Molecular Mechanisms of Neurotransmitter Release

Part of the book series: Advances in Neurobiology ((NEUROBIOL,volume 33))

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Abstract

Calcium (Ca2+) plays a critical role in triggering all three primary modes of neurotransmitter release (synchronous, asynchronous, and spontaneous). Synaptotagmin1, a protein with two C2 domains, is the first isoform of the synaptotagmin family that was identified and demonstrated as the primary Ca2+ sensor for synchronous neurotransmitter release. Other isoforms of the synaptotagmin family as well as other C2 proteins such as the double C2 domain protein family were found to act as Ca2+ sensors for different modes of neurotransmitter release. Major recent advances and previous data suggest a new model, release-of-inhibition, for the initiation of Ca2+-triggered synchronous neurotransmitter release. Synaptotagmin1 binds Ca2+ via its two C2 domains and relieves a primed pre-fusion machinery. Before Ca2+ triggering, synaptotagmin1 interacts Ca2+ independently with partially zippered SNARE complexes, the plasma membrane, phospholipids, and other components to form a primed pre-fusion state that is ready for fast release. However, membrane fusion is inhibited until the arrival of Ca2+ reorients the Ca2+-binding loops of the C2 domain to perturb the lipid bilayers, help bridge the membranes, and/or induce membrane curvatures, which serves as a power stroke to activate fusion. This chapter reviews the evidence supporting these models and discusses the molecular interactions that may underlie these abilities.

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Acknowledgments

I thank Dr. Zhao-Wen Wang, Dr. Natalí L. Chanaday Ricagni, Dr. Rong Sun, Elena D Bagatelas, and Liana Wilson for comments on the manuscript. This work was supported by National Institutes of Health (NIH) grant R00MH113764.

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  1. Department of Cell and Developmental Biology, Vanderbilt Brain Institute, Vanderbilt University, Nashville, TN, USA

    Qiangjun Zhou

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    Zhao-Wen Wang

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Zhou, Q. (2023). Calcium Sensors of Neurotransmitter Release. In: Wang, ZW. (eds) Molecular Mechanisms of Neurotransmitter Release. Advances in Neurobiology, vol 33. Springer, Cham. https://doi.org/10.1007/978-3-031-34229-5_5

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