Sodium/calcium exchanger expression in the mouse and rat olfactory systems
Sodium/calcium exchanger expression in the mouse and rat olfactory systems
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DOI：
10.1002/cne.21290
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发表时间：
2007-04-20
影响因子：
2.5
通讯作者：
Margolis, Frank L.
中科院分区：
文献类型：
--
作者：
Pyrski, Martina;Koo, Jae Hyung;Margolis, Frank L.
钠/钙 (Na+/Ca2+) 交换器是调节许多真核细胞中 Ca2+ 稳态的膜转运系统。在嗅觉和犁鼻感觉神经元中，配体诱导的嗅觉信号转导与细胞内 Ca2+ [Ca2+](i) 的流入和升高有关。虽然人们在嗅觉化学感觉神经元 (OSN) 的 Ca2+ 相关兴奋和适应事件的表征方面付出了很多努力，但对于将 [Ca2+](i) 返回到静息状态的机制知之甚少。为了鉴定参与小鼠 OSN 刺激后 Ca2+ 清除的蛋白质，我们分析了三种钾 (K+) 独立型 (NCX1, 2, 3) 和三种 K+ 依赖性 (NCKX1, 2, 3) Na+/Ca2+ 交换剂的表达。原位杂交表明，所有六种 Na+/Ca2+ 交换剂的 mRNA 共存于嗅觉和犁鼻系统的神经元中，并且有些在胚胎中已可检测到。其中，NCX1 和 NCKX1 分别代表丰度最高和最低的 mRNA。此外，免疫组织化学显示NCX1、2和3蛋白在嗅上皮、犁鼻器、Masera间隔器和Grueneberg神经节的几乎所有神经元中表达。这三种交换蛋白在 OSN 的树突、旋钮和质膜以及支持细胞中表现出不同的表达谱。此外，我们发现大鼠嗅粘膜中的 NCX1 mRNA 表达为 8 种选择性剪接变体。这是对哺乳动物嗅觉系统中 Na+/Ca2+ 交换器表达的首次全面分析。我们的结果表明，OSN 的 Ca2+ 挤出利用了多种不同的 Na+/Ca2+ 交换剂，并且不同的亚型针对不同的亚细胞区室。
Sodium/calcium (Na+/Ca2+) exchangers are membrane transport systems that regulate Ca2+-homeostasis in many eukaryotic cells. In olfactory and vomeronasal sensory neurons ligand-induced olfactory signal transduction is associated with influx and elevation of intracellular Ca2+, [Ca2+](i). While much effort has been devoted to the characterization of Ca2+-related excitation and adaptation events of olfactory chemosensory neurons (OSNs), much less is known about mechanisms that return [Ca2+](i) to the resting state. To identify proteins participating in the poststimulus Ca2+-clearance of mouse OSNs, we analyzed the expression of three potassium (K+)-independent (NCX1, 2, 3) and three K+-dependent (NCKX1, 2, 3) Na+/Ca2+ exchangers. In situ hybridization showed that mRNAs of all six Na+/Ca2+ exchangers coexist in neurons of the olfactory and vomeronasal systems, and that some are already detectable in the embryo. Of these, NCX1 and NCKX1 represent the most and least abundant mRNAs, respectively. Moreover, immunohistochemistry revealed that the NCX1, 2, and 3 proteins are expressed in nearly all neurons of the olfactory epithelium, the vomeronasal organ, the septal organ of Masera, and the Grueneberg ganglion. These three exchanger proteins display different expression profiles in dendrites, knobs, and plasma membranes of OSNs and in sustentacular cells. Furthermore, we show that NCX1 mRNA in rat olfactory mucosa is expressed as 8 alternative splice variants. This is the first comprehensive analysis of Na+/Ca2+ exchanger expression in the mammalian olfactory system. Our results suggest that Ca2+-extrusion by OSNs utilizes multiple different Na+/ Ca2+ exchangers and that different subtypes are targeted to different subcellular compartments.