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果蝇血清素转运蛋白dSERT异位表达后体内血清素储存的细胞类型特异性限制

Cell-type-specific limitation on in vivo serotonin storage following ectopic expression of the Drosophila serotonin transporter, dSERT.

作者信息

Park Sang Ki, George Rebecca, Cai Ying, Chang H Y, Krantz D E, Friggi-Grelin Florence, Birman Serge, Hirsh Jay

机构信息

Department of Biology, University of Virginia, Charlottesville, Virginia 22904, USA.

出版信息

J Neurobiol. 2006 Apr;66(5):452-62. doi: 10.1002/neu.20222.

Abstract

The synaptic machinery for neurotransmitter storage is cell-type specific. Although most elements of biosynthesis and transport have been identified, it remains unclear whether additional factors may be required to maintain this specificity. The Drosophila serotonin transporter (dSERT) is normally expressed exclusively in serotonin (5-HT) neurons in the CNS. Here we examine the effects of ectopic transcriptional expression of dSERT in the Drosophila larval CNS. We find a surprising limitation on 5-HT storage following ectopic expression of dSERT and green fluorescence protein-tagged dSERT (GFP-dSERT). When dSERT transcription is driven ectopically in the CNS, 5-HT is detectable only in 5-HT, dopamine (DA), and a very limited number of additional neurons. Addition of exogenous 5-HT does not dramatically broaden neuronal storage sites, so this limitation is only partly due to restricted intercellular diffusion of 5-HT. Furthermore, this limitation is not due to gross mislocalization of dSERT, because cells lacking or containing 5-HT show similar levels and subcellular distribution of GFP-dSERT protein, nor is it due to lack of the vesicular transporter, dVMAT. These data suggest that a small number of neurons selectively express factor(s) required for 5-HT storage, and potentially for function of dSERT.

摘要

用于神经递质储存的突触机制具有细胞类型特异性。尽管生物合成和运输的大多数元件已被鉴定,但尚不清楚是否需要其他因素来维持这种特异性。果蝇血清素转运体(dSERT)通常仅在中枢神经系统的血清素(5-HT)神经元中表达。在这里,我们研究了dSERT在果蝇幼虫中枢神经系统中的异位转录表达的影响。我们发现dSERT和绿色荧光蛋白标记的dSERT(GFP-dSERT)异位表达后,5-HT储存存在令人惊讶的限制。当dSERT转录在中枢神经系统中异位驱动时,仅在5-HT、多巴胺(DA)和极少数其他神经元中可检测到5-HT。添加外源性5-HT并不会显著拓宽神经元储存位点,因此这种限制仅部分归因于5-HT的细胞间扩散受限。此外,这种限制不是由于dSERT的严重错误定位,因为缺乏或含有5-HT的细胞显示出相似水平和亚细胞分布的GFP-dSERT蛋白,也不是由于缺乏囊泡转运体dVMAT。这些数据表明,少数神经元选择性地表达5-HT储存所需的因子,可能也表达dSERT功能所需的因子。

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