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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 孔繁璐(Fan-Lu Kung) | |
dc.contributor.author | Wen-Yan Chang | en |
dc.contributor.author | 張文彥 | zh_TW |
dc.date.accessioned | 2021-06-17T00:30:50Z | - |
dc.date.available | 2017-03-02 | |
dc.date.copyright | 2012-03-02 | |
dc.date.issued | 2012 | |
dc.date.submitted | 2012-02-13 | |
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dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/66335 | - |
dc.description.abstract | ANKS1B (Ankyrin Repeat and Sterile Alpha Motif Domain-containing Protein 1B)表現於大腦組織,是一種會與APP (Amyloid precursor protein)產生交互作用、並參與神經突觸到細胞核訊息傳導的蛋白質。過去研究指出,若以NMDA刺激大腦皮質初代神經細胞,會造成ANKS1B斷裂。接著N端ANKS1B會進入核中並且影響核內蛋白質的生成,C端ANKS1B則會停留在細胞質。為了探討APP在ANKS1B入核過程所扮演之角色,我們建構了幾個ANKS1B和APP的突變蛋白,並將其轉染至SH-SY5Y細胞表現。我們發現去除N端後的ANKS1B,即使在NMDA刺激後也會停留在細胞質不會進入核中。而去除C端的ANKS1B,即使在沒有NMDA刺激的情況下也會進到核內。而去在失去與APP的交互作用後,ANKS1B在NMDA刺激後也不會發生入核現象。這些初步的研究結果指出,ANKS1B藉由其C端的序列停留在膜上,而N端序列則會造成其進入核中,與APP的交互作用則在NMDA誘導的ANKS1B入核扮演重要角色。我們也嘗試尋找參與在入核過程中,造成ANKS1B發生斷裂的蛋白酶。calpain是一個會被鈣離子活化的蛋白酶。我們的結果指出,NMDA刺激會造成calpain的活化。但若先以calapin抑制劑ALLN處理後,calpain則會被抑制;而當calpain被抑制後,ANKS1B的入核現象也會受到抑制。這個結果指出calpain可能參與在ANKS1B的入核過程。我們也發現,ANKS1B可以經由一個不需外加鈣離子的路徑,在NMDA刺激後進入核內,在這條件下calpain仍有觀察到活化現象;而ALLN也會影響APP的processing。因此,calpain在ANKS1B入核過程所扮演的角色仍有待釐清。 | zh_TW |
dc.description.abstract | ANKS1B (Ankyrin Repeat and Sterile Alpha Motif Domain-containing Protein 1B) is a protein abundant in normal human tissues of brain. It is interacted with Amyloid precursor protein (APP) and proposed to be involved in synapse-to-nucleus signaling. Previous study has indicated NMDA stimulation induces the cleavage of ANKS1B in primary neuronal cultures. Then the N-terminal fragment shuttles to the nucleus and mediates protein synthesis, while the C-terminal fragment remains in the cytoplasm. To clarify the role of APP in nuclear translocation of ANKS1B, we constructed several ANKS1B and APP mutant plasmids, and transfected to SH-SY5Y. We found N-terminal truncated ANKS1B (C-ANK) remained in the cytoplasm even after NMDA stimulation, while C-terminal truncated one (N-ANK) could enter the nucleus without NMDA stimulation. In other hand, NMDA stimulation could not induce nuclear translocation when ANKS1B was not interacted with APP. These preliminary results suggested C-terminal sequence make ANKS1B retain on the membrane, while N-terminal sequence leads it to enter the nucleus. The interaction of APP was crucial in NMDA-mediated ANKS1B nuclear translocation. We also tried to find the protease involved in ANKS1B nuclear translocation. Calpain is a calcium-dependant enzyme. Our results showed calpain was activated after NMDA stimulation, and the treatment of ALLN, which was an inhibitor of calpain, blocked nuclear translocation of ANKS1B. It indicated calpain might be involved in ANKS1B nuclear translocation. We also found ANKS1B could shuttle to the nucleus in a extracellular-calcium- independent manner. And ALLN could influence APP processing. Therefore, the role of calpain in ANKS1B nuclear translocation was still remained to be clarified. | en |
dc.description.provenance | Made available in DSpace on 2021-06-17T00:30:50Z (GMT). No. of bitstreams: 1 ntu-101-R97423015-1.pdf: 1633055 bytes, checksum: fe3217a5571050b080fc3d70998d8286 (MD5) Previous issue date: 2012 | en |
dc.description.tableofcontents | 摘要...................................... 1
Abstract................................. 2 Abbreviations............................ 4 Introduction 1. Overview of ANKS1B ................... 7 2. Interaction of ANKS1B and PSD ........ 9 3. MDA stimulation ...................... 11 4. Interaction of ANKS1B and APP ........ 12 5. Calpain .............................. 14 Objective ............................... 16 Materials and Methods ................... 16 Results ................................. 24 Discussion .............................. 32 Figures ................................. 39 Appendix ................................ 60 References .............................. 63 | |
dc.language.iso | en | |
dc.title | APP與Calpain在NMDA所誘導的ANKS1B入核所扮演之角色 | zh_TW |
dc.title | Role of APP and calpain in NMDA-mediated ANKS1B nuclear translocation | en |
dc.type | Thesis | |
dc.date.schoolyear | 100-1 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 邱麗珠(Lih-Chu Chiou),顧記華(Jih-Hwa Guh) | |
dc.subject.keyword | APP,Calpain,ANKS1B,NMDA,入核, | zh_TW |
dc.subject.keyword | APP,Calpain,ANKS1B,NMDA,nuclear translocation, | en |
dc.relation.page | 67 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2012-02-13 | |
dc.contributor.author-college | 醫學院 | zh_TW |
dc.contributor.author-dept | 藥學研究所 | zh_TW |
顯示於系所單位: | 藥學系 |
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