Distribution and synaptic localization of nicotinic acetylcholine receptors containing a novel alpha7 subunit isoform in embryonic rat cortical neurons.
Distribution and synaptic localization of nicotinic acetylcholine receptors containing a novel alpha7 subunit isoform in embryonic rat cortical neurons.
复制标题
含有新型 α7 亚基亚型的烟碱乙酰胆碱受体在胚胎大鼠皮层神经元中的分布和突触定位。
DOI：
10.1016/j.neulet.2004.09.020
复制
发表时间：
2004
影响因子：
2.5
通讯作者：
Cuevas,Javier
中科院分区：
文献类型：
--
作者：
Severance,EmilyG;Cuevas,Javier
先前发现含有 α7 亚基亚型 α7-2 (α7-2-nAChRs) 的神经元烟碱乙酰胆碱受体 (nAChR) 可以形成功能性同五聚体通道，该通道缓慢脱敏并以快速可逆的方式结合 α-银环蛇毒素 (αBgt)。该亚型在天然受体的胞外配体结合域中整合了一个新的盒式外显子。尽管这种 α7 亚基亚型已在外周神经节和中枢神经系统中检测到，但人们对 α7-2-nAChR 的细胞功能知之甚少。使用针对盒式外显子氨基酸序列产生的多克隆抗体 (Ab 87) 并结合 (1) 识别所有已知 α7-nAChR 的抗体、(2) αBgt 和 (3) 针对多种细胞标记物的抗体，在胚胎大鼠培养的皮层神经元模型中进行共定位免疫细胞化学研究。基于 mAb319 和 αBgt 信号的共同分布，α7-2-nAChR 表达模式总体上与 α7 染色一致。然而，α7-2-nAChR 清楚地代表了 α7 受体的一个独特子集。 α7-2-nAChR 亚型遍布整个细胞体表面，并且定位于树突亚群。在突触后密度处观察到突触 α7-2 靶向的点状染色特征，并在突触前位置间歇性地观察到。 α7-2 亚基在 GABA 能和非 GABA 能神经元上都有表达。这些研究表明，含有 α7-2 亚基的受体构成了 α7-nAChR 的一个亚群，并可能参与中枢神经元突触发育过程中的细胞间信号传导。
Neuronal nicotinic acetylcholine receptors (nAChRs) containing the α7 subunit isoform, α7-2 (α7-2-nAChRs), have previously been found to form functional homopentameric channels that desensitize slowly and bind α-bungarotoxin (αBgt) in a rapidly reversible manner. This isoform incorporates a novel cassette exon in the extracellular, ligand binding domain of the native receptor. Although this α7 subunit isoform has been detected in peripheral ganglia as well as in the central nervous system, little is known about the cellular function of α7-2-nAChRs. Co-localization immunocytochemical studies were conducted in an embryonic rat cultured cortical neuron model using a polyclonal antibody (Ab 87) raised against the amino acid sequence of the cassette exon, in combination with (1) an antibody that recognizes all known α7-nAChRs, (2) αBgt, and (3) antibodies directed against multiple cellular markers. The pattern of α7-2-nAChR expression was consistent with α7 staining in general, based on co-distribution of mAb319 and αBgt signals. However, α7-2-nAChRs clearly represent a distinct subset of α7 receptors. The α7-2-nAChR subtype was found throughout the cell-soma surface and was localized to a subpopulation of dendrites. Punctate staining characteristic of synaptic α7-2 targeting was observed at post-synaptic densities and intermittently at pre-synaptic locations. The α7-2 subunit was expressed on both GABAergic and non-GABAergic neurons. These studies reveal that receptors containing the α7-2 subunit constitute a subpopulation of α7-nAChRs and likely participate in cell-to-cell signaling in developing synapses of central neurons.