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標題: | ANKS1B與APP之間的交互作用與NMDA受器訊息傳遞之相關性研究 Correlation study of NMDA receptor signaling and the interaction between ANKS1B and APP |
作者: | Fei-Yang Tzou 鄒飛洋 |
指導教授: | 孔繁璐(Fan-Lu Kung) |
關鍵字: | NMDA受器,ANKS1B,阿茲海默氏症, NMDA receptor,ANKS1B,APP,AICD, |
出版年 : | 2017 |
學位: | 碩士 |
摘要: | N-methyl-D-aspartate receptor (NMDAR) 是很重要的神經受器,它參與了許多神經的功能,例如神經突觸的可塑性、神經分化、學習,與記憶等功能。NMDA受器在結構、位置,以及功能上的多樣性,造就了它大量與複雜的訊息傳遞。NMDA受器的訊息傳遞相關的作用因子,在神經突觸後的位置聚集、彼此合作以完成相關的神經活動,或進一步將訊息傳遞下去。而其中一個作用因子,是蛋白質ankyrin repeat and sterile alpha motif domain-containing protein 1B (ANKS1B)。ANKS1B是後突觸質密區的骨架蛋白,在NMDA受器的活化之下,ANKS1B發生轉位入核的活動,並藉此調控了細胞整體的蛋白合成。相對於NMDAR對ANKS1B的影響,研究也發現ANKS1B參與了NMDAR次單位的運輸。此外,ANKS1B又稱作amyloid precursor protein Intracellular Domain Associated protein 1 (AIDA-1),取名自它與amyloid precursor protein intracellular domain (AICD)之間的交互作用,然而此交互作用的重要性尚無人探討。在此研究當中,試圖找出AICD和ANKS1B之間的交互作用,與NMDA受器訊息傳遞的相關性。本研究在SH-SY5Y神經瘤細胞株中,表現野生型 (wild-type) 或突變後失去與AICD交互作用的ANKS1B蛋白,並活化NMDA受器,觀察其在細胞核、質之間的活動;此外,本研究觀察表現野生型或突變後失去與AICD交互作用的ANKS1B,對於NMDA受器次單元的mRNA的表現量有何影響。初步的結果顯示,當ANKS1B失去與AICD的交互作用時,在細胞核內的表現量會上升。另一方面,在SH-SY5Y細胞中大量表現ANKS1B對NMDA受器的基因轉錄並沒有顯著的影響。 N-methyl-D-aspartate (NMDA) receptors are crucial for many neuronal functions, and the structural, local, and functional diversities of NMDARs contributes to its tremendous signaling pathways. At post-synapse, effectors of NMDAR signaling gather and coordinate with each other, regulating specific cellular processes and/or passing up the signaling cascades. One of the effectors of NMDAR is ANKS1B, a scaffold protein of post-synaptic density (PSD), which translocates into nucleus upon NMDAR stimulation and regulates protein synthesis. Besides being a downstream effector of NMDAR signaling, ANKS1B was found to control the transport of NMDAR subunits. On the other hand, ANKS1B interacts with intracellular domain of amyloid precursor protein (AICD), yet the physiological significance of this partnership remain unknown. Here, we wanted to identify the role of ANKS1B-AICD interaction in specific NMDAR signaling. We observed the nuclear localization of overexpressed wild-type or mutant ANKS1B without AICD interaction upon NMDAR stimulation in SH-SY5Y cells. In addition, we evaluate the effect of overexpressing wildtype or mutant ANKS1B on the expression profiles of NMDAR subunits. Preliminary results showed that the interaction between AICD and ANKS1B might regulate the nuclear localization of ANKS1B; moreover, overexpression of ANKS1B had no significant effect on transcription profile of NMDA receptor subunits. |
URI: | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/59168 |
DOI: | 10.6342/NTU201600152 |
全文授權: | 有償授權 |
顯示於系所單位: | 藥學系 |
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