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Calcineurin and Its Role in Synaptic Transmission

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Abstract

Calcineurin (CaN) is a serine/threonine phosphatase widely expressed in different cell types and structures including neurons and synapses. The most studied role of CaN is its involvement in the functioning of postsynaptic structures of central synapses. The role of CaN in the presynaptic structures of central and peripheral synapses is less understood, although it has generated a considerable interest and is a subject of a growing number of studies. The regulatory role of CaN in synaptic vesicle endocytosis in the synapse terminals is actively studied. In recent years, new targets of CaN have been identified and its role in the regulation of enzymes and neurotransmitter secretion in peripheral neuromuscular junctions has been revealed. CaN is the only phosphatase that requires calcium and calmodulin for activation. In this review, we present details of CaN molecular structure and give a detailed description of possible mechanisms of CaN activation involving calcium, enzymes, and endogenous and exogenous inhibitors. Known and newly discovered CaN targets at pre-and post-synaptic levels are described. CaN activity in synaptic structures is discussed in terms of functional involvement of this phosphatase in synaptic transmission and neurotransmitter release.

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Abbreviations

AID:

autoinhibitory domain

AKAP:

protein kinase A anchoring protein

AMPA:

α-amino-3-hydroxy-5-methyl-4-isoxazolpropionic acid

CaM:

calmodulin

CaMKII:

calcium/calmodulin-dependent type II kinase

CaN:

calcineurin

CaN-A:

calcineurin catalytic subunit

CaN-B:

calcineurin regulatory subunit

CDK5:

cyclin-dependent kinase 5

CREB:

cAMP-response element-binding protein

CsA:

cyclosporine A

EPP:

end-plate potential

FK506:

tacrolimus

FKBP12:

FK506-binding protein

GABA:

γ-aminobutyric acid

GAP43:

neuromodulin

I-1:

endogenous inhibitor of protein phosphatase 1

LTD:

long-term depression

LTP:

long-term potentiation

NFAT:

nuclear factor of activated T cells

NMDA:

N-methyl-D-aspartate

PKA:

protein kinase A

PKC:

protein kinase C

PP1:

protein phosphatase 1

RCAN:

calcineurin regulatory protein

TRPV1:

transient receptor potential cation channel subfamily V member 1

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Authors and Affiliations

  1. Lomonosov Moscow State University, Faculty of Biology, 119991, Moscow, Russia

    E. O. Tarasova, A. E. Gaydukov & O. P. Balezina

  2. Pirogov Russian National Research Medical University, 117997, Moscow, Russia

    A. E. Gaydukov

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  1. E. O. Tarasova
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Original Russian Text © E. O. Tarasova, A. E. Gaydukov, O. P. Balezina, 2018, published in Biokhimiya, 2018, Vol. 83, No. 6, pp. 852-869.

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Tarasova, E.O., Gaydukov, A.E. & Balezina, O.P. Calcineurin and Its Role in Synaptic Transmission. Biochemistry Moscow 83, 674–689 (2018). https://doi.org/10.1134/S0006297918060056

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