Presynaptic α2δ-2 Calcium Channel Subunits Regulate Postsynaptic GABAA Receptor Abundance and Axonal Wiring

Stefanie Geisler, Clemens L Schöpf, Ruslan Stanika, Marcus Kalb, Marta Campiglio, Daniele Repetto, Larissa Traxler, Markus Missler, Gerald J Obermair

Publikation: Beitrag in Fachzeitschrift (peer-reviewed)Artikel in Fachzeitschrift

29 Zitate (Scopus)

Abstract

Presynaptic α 2δ subunits of voltage-gated calcium channels regulate channel abundance and are involved in glutamatergic synapse formation. However, little is known about the specific functions of the individual α 2δ isoforms and their role in GABAergic synapses. Using primary neuronal cultures of embryonic mice of both sexes, we here report that presynaptic overexpression ofα 2δ-2 in GABAergic synapses strongly increases clustering of postsynaptic GABA ARs. Strikingly, presynaptic α 2δ-2 exerts the same effect in glutamatergic synapses, leading to a mismatched localization of GABA ARs. This mismatching is caused by an aberrant wiring of glutamatergic presynaptic boutons with GABAergic postsynaptic positions. The trans-synaptic effect ofα 2δ-2 is independent of the prototypical cell-adhesion molecules α-neurexins (α-Nrxns); however, α-Nrxns together with α 2δ-2 can modulate postsynaptic GABA AR abundance. Finally, exclusion of the alternatively spliced exon 23 of α 2δ-2 is essential for the trans-synaptic mechanism. The novel function of α 2δ-2 identified here may explain how abnormal α 2δ subunit expression can cause excitatory-inhibitory imbalance often associated with neuropsychiatric disorders.

OriginalspracheEnglisch
Seiten (von - bis)2581-2605
Seitenumfang25
FachzeitschriftJournal of Neuroscience
Jahrgang39
Ausgabenummer14
DOIs
PublikationsstatusVeröffentlicht - 03 Apr. 2019
Extern publiziertJa

ASJC Scopus Sachgebiete

  • Allgemeine Neurowissenschaft

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