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Do fragments of the neural cell adhesion molecule NCAM with or without attached polysialic acid differentially regulate transcription?

带有或不带有聚唾液酸的神经细胞粘附分子 NCAM 片段是否会差异调节转录？

基本信息

批准号：
250721355
负责人：
Professorin Dr. Melitta Schachner
金额：
--
依托单位：
Seniorgruppe Biosynthese Neuraler Strukturen
依托单位国家：
德国
项目类别：
Research Grants
财政年份：
2013
资助国家：
德国
起止时间：
2012-12-31 至 2015-12-31
项目状态：
已结题

来源：
https://gepris.dfg.de/gepris/projekt/250721355?language=en
关键词：
Do fragments neural cell adhesion

项目摘要

The aims of the proposed studies are the analysis of the functional roles of the transmembrane neural cell adhesion molecule NCAM and its associated glycan polysialic acid (PSA) in regulating transcription. In preliminary experiments we showed that function-triggering antibodies against NCAM elicit changes in the expression pattern of genes and that proteolytic NCAM fragments reach the nucleus. These NCAM fragments comprise not only the intracellular, but remarkably also the transmembrane and part of the extracellular domains. The hypothesis is that transcription of genes is different in the presence or absence of fragment-associated PSA due to the different association of PSA-carrying and -lacking NCAM fragments with transcription factors or chromatin-associated molecules. We propose that PSA-modulated transcriptional regulation depends on the differentiation state of cells - with PSA being characteristic of more immature neurons. We also propose that transcriptional regulation by PSA-carrying and -lacking NCAM fragments is different from that induced by the known signal transduction pathways. The differentially transcribed genes will be identified and validated at the mRNA and protein levels, and their functions will be analyzed via established cell biological methods in vitro. These experiments should allow first insights into the functional potential of glycans attached to adhesion molecule fragments in the nucleus.

拟开展的研究的目的是分析跨膜神经细胞粘附分子NCAM及其相关的聚糖聚唾液酸（PSA）在调节转录中的功能作用。在初步实验中，我们发现，功能触发抗体对NCAM引起的基因表达模式的变化，蛋白水解NCAM片段到达细胞核。这些NCAM片段不仅包含胞内结构域，而且显著地包含跨膜结构域和部分胞外域。该假设是，基因的转录是不同的片段相关的PSA的存在或不存在下，由于PSA携带和缺乏NCAM片段与转录因子或染色质相关分子的不同协会。我们认为PSA调节的转录调控依赖于细胞的分化状态，PSA是更不成熟神经元的特征。我们还提出，PSA携带和缺乏NCAM片段的转录调控是不同的，从已知的信号转导途径诱导。将在mRNA和蛋白质水平鉴定和验证差异转录的基因，并通过体外建立的细胞生物学方法分析其功能。这些实验应该允许第一次深入了解聚糖附着在细胞核中的粘附分子片段的功能潜力。