Neuronal Ca2+ sensor VILIP-1 leads to the upregulation of functional alpha4beta2 nicotinic acetylcholine receptors in hippocampal neurons.
Neuronal Ca2+ sensor VILIP-1 leads to the upregulation of functional alpha4beta2 nicotinic acetylcholine receptors in hippocampal neurons.
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DOI：
10.1016/j.mcn.2008.11.001
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发表时间：
2009-02
影响因子：
3.5
通讯作者：
Braunewell, K. H.
中科院分区：
文献类型：
--
作者：
Zhao, C. J.;Noack, C.;Brackmann, M.;Gloveli, T.;Maelicke, A.;Heinemann, U.;Anand, R.;Braunewell, K. H.
研究表明，神经元钙离子感受器蛋白VILIP-1可与烟碱乙酰胆碱受体α4-亚基的胞质环相互作用，α4β2烟碱乙酰胆碱受体是脑内含量最高的烟碱乙酰胆碱受体亚型，对尼古丁具有高亲和力。α-4-β-2nAChR在尼古丁成瘾和尼古丁对认知的有益影响中起着至关重要的作用。它的功能障碍与额叶癫痫、阿尔茨海默病和精神分裂症有关。在这里，我们报道过表达VILIP-1增强了ACh的反应性，而针对VILIP-1的小干扰RNA降低了海马神经元的α4β2nAchR电流。其潜在的分子机制可能涉及VILIP-1介导的α-4、β-2nAChRs构件性胞吐增强。这两个相互作用伙伴以钙离子依赖的方式与参与跨高尔基体膜运输的高尔基体陷阱蛋白-6共同定位。因此，我们推测，VILIP-1表达的调节可能调节了配体门控离子通道的表面表达，如α4β2nAChRs，可能包括一种新的配体门控离子通道的生理上调形式。
The neuronal Ca2+-sensor protein VILIP-1, known to affect clathrin-dependent receptor trafficking, has been shown to interact with the cytoplasmic loop of the α4-subunit of the α4β2 nicotinic acetylcholine receptor (nAChR), which is the most abundant nAChR subtype with high-affinity for nicotine in the brain. The α4β2 nAChR is crucial for nicotine addiction and the beneficial effects of nicotine on cognition. Its dysfunction has been implicated in frontal lobe epilepsy, Alzheimer’s disease and schizophrenia. Here we report that overexpression of VILIP-1 enhances ACh responsiveness, whereas siRNA against VILIP-1 reduces α4β2 nAChR currents of hippocampal neurons. The underlying molecular mechanism likely involves enhanced constitutive exocytosis of α4β2 nAChRs mediated by VILIP-1. The two interaction partners co-localize in a Ca2+-dependent manner with syntaxin-6, a Golgi-SNARE protein involved in trans-Golgi membrane trafficking. Thus, we speculate that regulation of VILIP-1-expression might modulate surface expression of ligand-gated ion channels, such as the α4β2 nAChRs, possibly comprising a novel form of physiological up-regulation of ligand-gated ion channels.
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影响因子：
34.7
作者：
Burgoyne, Robert D.
通讯作者：
Burgoyne, Robert D.
影响因子：
4.7
作者：
Braunewell, KH;Brackmann, M;Manahan-Vaughan, D
通讯作者：
Manahan-Vaughan, D
影响因子：
3.3
作者：
Davanger, S;Bock, JB;Scheller, RH
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Scheller, RH
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7.6
作者：
Breese, CR;Lee, MJ;Leonard, S
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Leonard, S
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2.5
作者：
Alkondon, M;Albuquerque, EX
通讯作者：
Albuquerque, EX