Thalhammer, A;
Contestabile, A;
Ermolyuk, YS;
Ng, T;
Volynski, KE;
Soong, TW;
Goda, Y;
(2017)
Alternative Splicing of P/Q-Type Ca2+ Channels Shapes Presynaptic Plasticity.
Cell Reports
, 20
(2)
pp. 333-343.
10.1016/j.celrep.2017.06.055.
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Abstract
Alternative splicing of pre-mRNAs is prominent in the mammalian brain, where it is thought to expand proteome diversity. For example, alternative splicing of voltage-gated Ca2+ channel (VGCC) α1 subunits can generate thousands of isoforms with differential properties and expression patterns. However, the impact of this molecular diversity on brain function, particularly on synaptic transmission, which crucially depends on VGCCs, is unclear. Here, we investigate how two major splice isoforms of P/Q-type VGCCs (Cav2.1[EFa/b]) regulate presynaptic plasticity in hippocampal neurons. We find that the efficacy of P/Q-type VGCC isoforms in supporting synaptic transmission is markedly different, with Cav2.1[EFa] promoting synaptic depression and Cav2.1[EFb] synaptic facilitation. Following a reduction in network activity, hippocampal neurons upregulate selectively Cav2.1[EFa], the isoform exhibiting the higher synaptic efficacy, thus effectively supporting presynaptic homeostatic plasticity. Therefore, the balance between VGCC splice variants at the synapse is a key factor in controlling neurotransmitter release and presynaptic plasticity.
| Type: | Article |
|---|---|
| Title: | Alternative Splicing of P/Q-Type Ca2+ Channels Shapes Presynaptic Plasticity |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.celrep.2017.06.055 |
| Publisher version: | http://doi.org/10.1016/j.celrep.2017.06.055 |
| Language: | English |
| Additional information: | Copyright © 2017 The Authors. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
| Keywords: | P/Q-type voltage-gated calcium channelsCav2.1alternative splicingshort-term synaptic plasticityrelease probabilityhomeostatic synaptic plasticityoptogeneticssynaptophysin-pHluorinGCaMPRNAi |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Clinical and Experimental Epilepsy |
| URI: | https://discovery.ucl.ac.uk/id/eprint/1567977 |
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