Functional interaction between Lypd6 and nicotinic acetylcholine receptors.
Functional interaction between Lypd6 and nicotinic acetylcholine receptors.
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LYPD6和烟碱乙酰胆碱受体之间的功能相互作用。
DOI：
10.1111/jnc.13718
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发表时间：
2016-09
影响因子：
4.7
通讯作者：
Thomsen MS
中科院分区：
文献类型：
--
作者：
Arvaniti M;Jensen MM;Soni N;Wang H;Klein AB;Thiriet N;Pinborg LH;Muldoon PP;Wienecke J;Imad Damaj M;Kohlmeier KA;Gondré-Lewis MC;Mikkelsen JD;Thomsen MS
烟碱型乙酰胆碱受体（nAChR）影响脑中的多种生理功能，并且它们的功能由Lynx家族的调节蛋白调节。在这里，我们首次报告了Lynx蛋白LY 6/PLAUR结构域6（Lypd 6）与人脑提取物中nAChR的直接相互作用，确定Lypd 6是nAChR功能的新型调节剂。使用蛋白质交联和亲和纯化从人类颞叶皮层提取物，我们证明Lypd 6是一种突触富集的膜结合蛋白，结合到多个nAChR亚型在人脑中。此外，可溶性重组Lypd 6蛋白减弱大鼠脑切片中尼古丁诱导的海马内向电流，并降低PC 12细胞中尼古丁诱导的细胞外信号调节激酶磷酸化，表明Lypd 6的结合足以抑制nAChR介导的细胞内信号传导。我们进一步表明，大鼠围产期尼古丁暴露（从胚胎第7天到纳塔尔后第21天，通过微型泵向母鼠给予4 mg/kg/天）显著增加了成年期海马体中Lypd 6蛋白水平，而这仅在成年期暴露于尼古丁后不会发生。我们的研究结果表明，Lypd 6是一种多功能的抑制剂胆碱能信号在大脑中，Lypd 6是失调的尼古丁暴露在早期发展。 Lynx家族的调节蛋白调节烟碱受体（nAChR）的功能。我们首次报道Lynx蛋白Lypd 6与人脑提取物中的nAChR结合，并且重组Lypd 6降低尼古丁诱导的ERK磷酸化并减弱尼古丁诱导的海马内向电流。我们的研究结果表明，Lypd 6是一种多功能的抑制剂胆碱能信号在大脑中。
Nicotinic acetylcholine receptors (nAChRs) affect multiple physiological functions in the brain and their functions are modulated by regulatory proteins of the Lynx family. Here, we report for the first time a direct interaction of the Lynx protein LY6/PLAUR domain‐containing 6 (Lypd6) with nAChRs in human brain extracts, identifying Lypd6 as a novel regulator of nAChR function. Using protein cross‐linking and affinity purification from human temporal cortical extracts, we demonstrate that Lypd6 is a synaptically enriched membrane‐bound protein that binds to multiple nAChR subtypes in the human brain. Additionally, soluble recombinant Lypd6 protein attenuates nicotine‐induced hippocampal inward currents in rat brain slices and decreases nicotine‐induced extracellular signal‐regulated kinase phosphorylation in PC12 cells, suggesting that binding of Lypd6 is sufficient to inhibit nAChR‐mediated intracellular signaling. We further show that perinatal nicotine exposure in rats (4 mg/kg/day through minipumps to dams from embryonic day 7 to post‐natal day 21) significantly increases Lypd6 protein levels in the hippocampus in adulthood, which did not occur after exposure to nicotine in adulthood only. Our findings suggest that Lypd6 is a versatile inhibitor of cholinergic signaling in the brain, and that Lypd6 is dysregulated by nicotine exposure during early development. Regulatory proteins of the Lynx family modulate the function of nicotinic receptors (nAChRs). We report for the first time that the Lynx protein Lypd6 binds to nAChRs in human brain extracts, and that recombinant Lypd6 decreases nicotine‐induced ERK phosphorylation and attenuates nicotine‐induced hippocampal inward currents. Our findings suggest that Lypd6 is a versatile inhibitor of cholinergic signaling in the brain.
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DOI：
10.1016/0169-328x(90)90003-v
发表时间：
1990-06-01
期刊：
MOLECULAR BRAIN RESEARCH
影响因子：
--
作者：
CRAY, C;KEANE, RW;LEVY, RB
通讯作者：
LEVY, RB
影响因子：
5.2
作者：
Chung, Brian H. Y.;Mullegama, Sureni;Mendoza-Londono, Roberto
通讯作者：
Mendoza-Londono, Roberto
影响因子：
2.5
作者：
Buhler, AV;Dunwiddie, TV
通讯作者：
Dunwiddie, TV
影响因子：
3.5
作者：
Dessaud, E;Salaün, D;deLapeyrière, O
通讯作者：
deLapeyrière, O
影响因子：
4.2
作者：
Carino, Charlene;Fibuch, Eugene E.;Mao, Li-Min;Wang, John Q.
通讯作者：
Wang, John Q.