Signaling by intracellular β2-adrenergic receptors regulates AMPA receptor trafficking and synaptic plasticity.

IF 7.5 1区 生物学 Q1 CELL BIOLOGY
Boram Lee, Xiaomin Xing, Erik A Hammes, Zhuoer Zeng, Zoila M Estrada-Tobar, Karam Kim, Kyle E Ireton, Kwun Nok Mimi Man, Ariel A Jacobi, Ruben A Berumen, Justin C Weiner, Ao Shen, Bing Xu, Joanne Wang, Paul J Gasser, Manuel F Navedo, Yang K Xiang, Elva Díaz, Chao-Yin Chen, Mary C Horne, Johannes W Hell
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引用次数: 0

Abstract

Signaling by norepinephrine (NE) via adrenergic receptors (ARs) mediates attention, yet the underlying molecular mechanisms are largely unknown. AMPA receptors (AMPARs) form a complex with β2ARs, Gs, adenylyl cyclase, and protein kinase A (PKA) to augment AMPAR phosphorylation and, thereby, surface expression. We show that signaling by intracellular β2ARs is required for these effects and two different forms of long-term potentiation (LTP) that depend on β2AR signaling and phosphorylation of the AMPAR GluA1 subunit on S845. Inhibition of two NE transporters, the organic cation transporter 3 (OCT3) and the plasma membrane monoamine transporter (PMAT), impairs phosphorylation of the AMPAR GluA1 subunit on S845 by PKA, GluA1 surface insertion, both forms of LTP, and upregulation of miniature excitatory postsynaptic currents upon injection of NE into neurons. These results provide strong evidence for signaling by NE upon its transport into neurons in general and specifically in synaptic plasticity.

细胞内β2-肾上腺素能受体的信号传导调节AMPA受体的转运和突触可塑性。
去甲肾上腺素(NE)通过肾上腺素能受体(ARs)介导注意力,但潜在的分子机制在很大程度上是未知的。AMPA受体(AMPARs)与β2ARs、Gs、腺苷酸环化酶和蛋白激酶a (PKA)形成复合物,增强AMPAR磷酸化,从而增加表面表达。我们发现细胞内β2AR信号是这些作用和两种不同形式的长期增强(LTP)所必需的,这些作用依赖于β2AR信号和AMPAR GluA1亚基在S845上的磷酸化。两种NE转运体,有机阳离子转运体3 (OCT3)和质膜单胺转运体(PMAT)的抑制,通过PKA、GluA1表面插入、两种形式的LTP以及向神经元注射NE后微兴奋性突触后电流的上调,损害AMPAR上S845上GluA1亚基的磷酸化。这些结果提供了强有力的证据,证明NE在其转运到神经元中的一般信号,特别是在突触可塑性中。
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来源期刊
Cell reports
Cell reports CELL BIOLOGY-
CiteScore
13.80
自引率
1.10%
发文量
1305
审稿时长
77 days
期刊介绍: Cell Reports publishes high-quality research across the life sciences and focuses on new biological insight as its primary criterion for publication. The journal offers three primary article types: Reports, which are shorter single-point articles, research articles, which are longer and provide deeper mechanistic insights, and resources, which highlight significant technical advances or major informational datasets that contribute to biological advances. Reviews covering recent literature in emerging and active fields are also accepted. The Cell Reports Portfolio includes gold open-access journals that cover life, medical, and physical sciences, and its mission is to make cutting-edge research and methodologies available to a wide readership. The journal's professional in-house editors work closely with authors, reviewers, and the scientific advisory board, which consists of current and future leaders in their respective fields. The advisory board guides the scope, content, and quality of the journal, but editorial decisions are independently made by the in-house scientific editors of Cell Reports.
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