Transient Confinement of CaV2.1 Ca2+-Channel Splice Variants Shapes Synaptic Short-Term Plasticity

Heck J, Parutto P, Ciuraszkiewicz A, Bikbaev A, Freund R, Mitlöhner J, Andres-Alonso M, Fejtová A, Holcman D, Heine M (2019)

Publication Type: Journal article

Publication year: 2019

Journal

Neuron Elsevier (Cell Press)

Book Volume: 103

Pages Range: 66-79.e12

Journal Issue: 1

DOI: 10.1016/j.neuron.2019.04.030

Abstract

The precision and reliability of synaptic information transfer depend on the molecular organization of voltage-gated calcium channels (VGCCs) within the presynaptic membrane. Alternative splicing of exon 47 affects the C-terminal structure of VGCCs and their affinity to intracellular partners and synaptic vesicles (SVs). We show that hippocampal synapses expressing VGCCs either with exon 47 (CaV2.1+47) or without (CaV2.1Δ47) differ in release probability and short-term plasticity. Tracking single channels revealed transient visits (∼100 ms) of presynaptic VGCCs in nanodomains (∼80 nm) that were controlled by neuronal network activity. Surprisingly, despite harboring prominent binding sites to scaffold proteins, CaV2.1+47 persistently displayed higher mobility within nanodomains. Synaptic accumulation of CaV2.1 was accomplished by optogenetic clustering, but only CaV2.1+47 increased transmitter release and enhanced synaptic short-term depression. We propose that exon 47-related alternative splicing of CaV2.1 channels controls synapse-specific release properties at the level of channel mobility-dependent coupling between VGCCs and SVs.

Authors with CRIS profile

Anna Fejtová Professur für Molekulare Psychiatrie

Involved external institutions

Leibniz-Institut für Neurobiologie (LIN) DE Germany (DE) École Normale Supérieure - PSL (ENS) FR France (FR)

How to cite

APA:

Heck, J., Parutto, P., Ciuraszkiewicz, A., Bikbaev, A., Freund, R., Mitlöhner, J.,... Heine, M. (2019). Transient Confinement of CaV2.1 Ca2+-Channel Splice Variants Shapes Synaptic Short-Term Plasticity. Neuron, 103(1), 66-79.e12. https://doi.org/10.1016/j.neuron.2019.04.030

MLA:

Heck, Jennifer, et al. "Transient Confinement of CaV2.1 Ca2+-Channel Splice Variants Shapes Synaptic Short-Term Plasticity." Neuron 103.1 (2019): 66-79.e12.

BibTeX: Download