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

被引：35

作者：

Geisler, Stefanie ^{[1
]}

Schoepf, Clemens L. ^{[1
]}

Stanika, Ruslan ^{[1
]}

Kalb, Marcus ^{[1
]}

Campiglio, Marta ^{[1
]}

Repetto, Daniele ^{[2
]}

Traxler, Larissa ^{[1
]}

Missler, Markus ^{[2
]}

Obermair, Gerald J. ^{[1
]}

机构：

[1] Med Univ Innsbruck, Div Physiol, A-6020 Innsbruck, Austria

[2] Westfalische Wilhelms Univ, Inst Anat & Mol Neurobiol, D-48149 Munster, Germany

来源：

JOURNAL OF NEUROSCIENCE | 2019年 / 39卷 / 14期

基金：

奥地利科学基金会;

关键词：

auxiliary subunits; cacna2d; cultured hippocampal neurons; imaging; immunocytochemistry; voltage-gated calcium channels; TARGETED DISRUPTION; EXCITATORY SYNAPSES; SURFACE DYNAMICS; DENDRITIC SPINES; ALPHA-NEUREXINS; MESSENGER-RNA; HIPPOCAMPAL; NERVE; GENE; EXPRESSION;

D O I：

10.1523/JNEUROSCI.2234-18.2019

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Presynaptic alpha(2)delta 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 alpha(2)delta isoforms and their role in GABAergic synapses. Using primary neuronal cultures of embryonic mice of both sexes, we here report that presynaptic overexpression of alpha(2)delta-2 in GABAergic synapses strongly increases clustering of postsynaptic GABA(A)Rs. Strikingly, presynaptic alpha(2)delta-2 exerts the same effect in glutamatergic synapses, leading to a mismatched localization of GABA(A)Rs. This mismatching is caused by an aberrant wiring of glutamatergic presynaptic boutons with GABAergic postsynaptic positions. The trans-synaptic effect of alpha(2)delta-2 is independent of the prototypical cell-adhesion molecules alpha-neurexins (alpha-Nrxns); however, alpha-Nrxns together with alpha(2)delta-2 can modulate postsynaptic GABA(A)R abundance. Finally, exclusion of the alternatively spliced exon 23 of alpha(2)delta-2 is essential for the trans-synaptic mechanism. The novel function of alpha(2)delta-2 identified here may explain how abnormal alpha(2)delta subunit expression can cause excitatory-inhibitory imbalance often associated with neuropsychiatric disorders.

引用

页码：2581 / 2605

页数：25

共 104 条

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