气候变化领域集成服务门户(CCPortal): Presynaptic α2δ subunits are key organizers of glutamatergic synapses

CCPortal

DOI	10.1073/pnas.1920827118
	Presynaptic α2δ subunits are key organizers of glutamatergic synapses
	Schöpf C.L.; Ablinger C.; Geisler S.M.; Stanika R.I.; Campiglio M.; Kaufmann W.A.; Nimmervoll B.; Schlick B.; Brockhaus J.; Missler M.; Shigemoto R.; Obermair G.J.
发表日期	2021
ISSN	00278424
卷号	118 期号:14
英文摘要	In nerve cells the genes encoding for α2δ subunits of voltage-gated calcium channels have been linked to synaptic functions and neurological disease. Here we show that α2δ subunits are essential for the formation and organization of glutamatergic synapses. Using a cellular α2δ subunit triple-knockout/knockdown model, we demonstrate a failure in presynaptic differentiation evidenced by defective presynaptic calcium channel clustering and calcium influx, smaller presynaptic active zones, and a strongly reduced accumulation of presynaptic vesicle-associated proteins (synapsin and vGLUT). The presynaptic defect is associated with the downscaling of postsynaptic AMPA receptors and the postsynaptic density. The role of α2δ isoforms as synaptic organizers is highly redundant, as each individual α2δ isoform can rescue presynaptic calcium channel trafficking and expression of synaptic proteins. Moreover, α2δ-2 and α2δ-3 with mutated metal iondependent adhesion sites can fully rescue presynaptic synapsin expression but only partially calcium channel trafficking, suggesting that the regulatory role of α2δ subunits is independent from its role as a calcium channel subunit. Our findings influence the current view on excitatory synapse formation. First, our study suggests that postsynaptic differentiation is secondary to presynaptic differentiation. Second, the dependence of presynaptic differentiation on α2δ implicates α2δ subunits as potential nucleation points for the organization of synapses. Finally, our results suggest that α2δ subunits act as transsynaptic organizers of glutamatergic synapses, thereby aligning the synaptic active zone with the postsynaptic density. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Cultured hippocampal neurons; Synapse formation; Synaptic calcium channels; Transsynaptic
语种	英语
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/179965
作者单位	Institute of Physiology, Medical University of Innsbruck, Innsbruck, A-6020, Austria; Department of Pharmacology and Toxicology, University of Innsbruck, Innsbruck, A-6020, Austria; Division of Physiology, Karl Landsteiner University of Health Sciences, Krems, A-3500, Austria; Institute of Science and Technology Austria, Klosterneuburg, A-3400, Austria; Institute of Anatomy and Molecular Neurobiology, Westfälische Wilhelms University, Münster, 48149, Germany
推荐引用方式 GB/T 7714	Schöpf C.L.,Ablinger C.,Geisler S.M.,et al. Presynaptic α2δ subunits are key organizers of glutamatergic synapses[J],2021,118(14).
APA	Schöpf C.L..,Ablinger C..,Geisler S.M..,Stanika R.I..,Campiglio M..,...&Obermair G.J..(2021).Presynaptic α2δ subunits are key organizers of glutamatergic synapses.Proceedings of the National Academy of Sciences of the United States of America,118(14).
MLA	Schöpf C.L.,et al."Presynaptic α2δ subunits are key organizers of glutamatergic synapses".Proceedings of the National Academy of Sciences of the United States of America 118.14(2021).