Nanoscale organization of CaV2.1 splice isoforms at presynaptic terminals: implications for synaptic vesicle release and synaptic facilitation

Lorenzo A Cingolani; Agnes Thalhammer; Fanny Jaudon; Jessica Muià; Gabriele Baj

doi:10.1515/hsz-2023-0235

Nanoscale organization of Ca_V2.1 splice isoforms at presynaptic terminals: implications for synaptic vesicle release and synaptic facilitation

Biol Chem. 2023 Sep 4;404(10):931-937. doi: 10.1515/hsz-2023-0235. Print 2023 Sep 26.

Authors

Lorenzo A Cingolani^{1

2}, Agnes Thalhammer^{1

3}, Fanny Jaudon^{1

4}, Jessica Muià¹, Gabriele Baj^{1

3}

Affiliations

¹ Department of Life Sciences, University of Trieste, via Giorgieri 5, I-34127 Trieste, Italy.
² Center for Synaptic Neuroscience and Technology (NSYN), Fondazione Istituto Italiano di Tecnologia (IIT), Largo Rosanna Benzi 10, I-16132 Genoa, Italy.
³ Centro Interdipartimentale di Microscopia Avanzata (CIMA), University of Trieste, via Fleming 31, I-34127 Trieste, Italy.
⁴ IRCCS Ospedale Policlinico San Martino, Largo Rosanna Benzi 10, I-16132 Genoa, Italy.

Abstract

The distance between Ca_V2.1 voltage-gated Ca²⁺ channels and the Ca²⁺ sensor responsible for vesicle release at presynaptic terminals is critical for determining synaptic strength. Yet, the molecular mechanisms responsible for a loose coupling configuration of Ca_V2.1 in certain synapses or developmental periods and a tight one in others remain unknown. Here, we examine the nanoscale organization of two Ca_V2.1 splice isoforms (Ca_V2.1[EFa] and Ca_V2.1[EFb]) at presynaptic terminals by superresolution structured illumination microscopy. We find that Ca_V2.1[EFa] is more tightly co-localized with presynaptic markers than Ca_V2.1[EFb], suggesting that alternative splicing plays a crucial role in the synaptic organization of Ca_V2.1 channels.

Keywords: CaV2.1; Munc13; alternative splicing; presynaptic terminals; structural illumination microscopy; voltage-gated Ca2+ channels.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Presynaptic Terminals*
Protein Isoforms
Synapses
Synaptic Vesicles*

Substances

voltage-dependent calcium channel (P-Q type)
Protein Isoforms