Review
Calcineurin regulation of synaptic function: from ion channels to transmitter release and gene transcription

https://doi.org/10.1016/S0165-6147(97)01046-8Get rights and content

Abstract

Calcineurin is a calcium (Ca2+)/calmodulin (CaM)-dependent protein phosphatase that has been shown to regulate the activity of ion channels, neurotransmitter and hormone release, synaptic plasticity and gene transcription. At glutamatergic synapses, the inhibition of calcineurin with immunosuppressant drugs has been reported to enhance both the presynaptic release of glutamate and postsynaptic responsiveness. Several other ligand- and voltage-gated ion channels are negatively regulated by calcineurin. Hormone release in insulin-secreting pancreatic β cells and pituitary corticotrope tumour (AtT20) cells is also negatively regulated by calcineurin. In this article, Jerrel Yakel discusses the evidence that calcineurin plays a vital role in regulating neuronal excitability and hormone release.

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      Although the precise function of this calcium signal is not well defined, it likely involves calcium sensors such as the calcium/calmodulin-dependent phosphatase calcineurin (also known as PP2B), the activity of which was required for eCB-LTD at both hippocampal and corticostriatal synapses (Andrade-Talavera et al., 2016; Cui et al., 2016; Heifets et al., 2008). Calcineurin is a serine/threonine phosphatase that is often associated with postsynaptic signalling and is involved in multiple pathways implicated in synaptic plasticity, one of which is the regulation of postsynaptically expressed VGCCs (L-type, CaV1.2/1.3) (Peterson et al., 1999; Yakel, 1997; Zuhlke et al., 1999). Both calcineurin and CaV1.2 exist in a molecular complex mediated by the scaffolding protein AKAP79/150 (A-Kinase anchoring proteins), which together with PKA and calmodulin bidirectionally regulate the activity of CaV1.2 (Dittmer et al., 2014; Oliveria et al., 2012).

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