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| ???org.dspace.app.webui.jsptag.ItemTag.dcfield??? | Value | Language |
|---|---|---|
| dc.contributor.advisor | 孔繁璐 | |
| dc.contributor.author | Wei-Lun Lin | en |
| dc.contributor.author | 林煒倫 | zh_TW |
| dc.date.accessioned | 2021-06-08T04:18:51Z | - |
| dc.date.copyright | 2010-09-13 | |
| dc.date.issued | 2010 | |
| dc.date.submitted | 2010-07-26 | |
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/22483 | - |
| dc.description.abstract | ANKS1B表現於成人的大腦與睪丸組織中，目前被認為可能與細胞內蛋白質的生成有關。因ANKS1B與第一型穿膜蛋白APP有交互作用，故ANKS1B又被稱為AIDA-1。過去的研究指出若以NMDA刺激會促使ANKS1B產生斷裂，而後N端片段移動至細胞核內而C端片段則留在細胞質中。在這裡我們想釐清APP processing是否影響ANKS1B進入細胞核。我們發現當使用DAPT處理SH-SY5Y抑制AICD從APP釋放時，NMDA刺激造成的ANKS1B進核現象會受到抑制。但是當在細胞內表現失去PTB domain與C端末端的ANKS1B時，則其不需經NMDA刺激即可進入細胞核中。當在細胞中大量表現含YENPTY序列的AICD，使其與膜上APP競爭與ANKS1B的交互作用，發現ANKS1B不需經NMDA刺激，即可進入核內。這些結果指出膜上APP對ANKS1B可能扮演anchor的角色。同時觀察到在大量表現AICD競爭時，進入核中的同樣只有N端的ANKS1B片段，我們因此假設APP對ANKS1B可能也具有保護的作用，當ANKS1B失去與APP除AICD外的其他部分的交互作用時，會使ANKS1B被細胞內某一種蛋白酶切割，而後產生的N端片段得以進入細胞核中。我們發現在NMDA刺激與大量表現free AICD時都會導致細胞內鈣離子濃度上升，在利用CaMPDB計算受鈣離子活化的蛋白酶calpains在ANKS1B上可能的作用位置後，發現若在第283個胺基酸後產生交互作用則產生出來的斷裂片段大小與受NMDA刺激產生出的片段大小相似，懷疑其可能為對ANKS1B作用的蛋白酶，目前的實驗結果顯示在NMDA刺激造成ANKS1B斷裂的條件下，未觀察到calpain活化態的產生。根據這些結果， APP在ANKS1B的進核現象中扮演著重要的角色，彼此的交互作用可能影響ANKS1B在細胞內的功能。 | zh_TW |
| dc.description.abstract | ANKS1B is detected in brain and testis in normal human tissues, it is proposed to regulate the protein synthesis. Because ANKS1B interacts with APP, it is also called APP intracellular domain associated protein-1. Past studies of ANKS1B indicate that NMDA stimulation induces the proteolytic cleavage of ANKS1B in primary neuronal cultures. The N-term fragment shuttles to the nucleus while the C-term fragment remains in the cytoplasm. We want to clarify the role of APP processing in NMDA-mediated translocation of ANKS1B. When SH-SY5Y cells were treated with DAPT (γ-secretase inhibitor) to block the release of AICD from APP, our result shows the translocation of ANKS1B was inhibited. However, ANKS1B losing its PTB binding domain and C-terminus can translocate to nucleus in the absence of NMDA stimulation. Interestingly, when YENPTY-containing AICD was overexpressed to compete for the interaction with ANKS1B, the translocation of ANKS1B was observed. These results suggest APP may be an anchor to attach ANKS1B to the membrane. We also noticed that the N-terminal ANKS1B fragment shuttles to nucleus when AICD was overexpressed. Therefore we hypothesized that APP may prevent the cleavage of ANKS1B and some proteases may be able to interact with ANKS1B once ANKS1B loses its interaction with APP. NMDA stimulation and AICD overexpression both can elevate the intracellular calcium concentration, and the prediction result reveals that if calpain interacts to the 283th amino acid of ANKS1B, the size of produced fragments are similar to NMDA stimulation. However, our result indicats no active form calpain is noticed after NMDA stimulation. According to these results, APP plays an important role in the translocation of ANKS1B. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-08T04:18:51Z (GMT). No. of bitstreams: 1 ntu-99-R97423009-1.pdf: 4066054 bytes, checksum: 4f71a7bc7645f767d9a4e393d26fbc9c (MD5) Previous issue date: 2010 | en |
| dc.description.tableofcontents | 口試委員會審定書I
誌謝II 中文摘要 III 英文摘要 IV 英文縮寫表 V 序論1 1.ANKS1B 1 2.PSD與ANKS1B間的交互作用3 3.NMDAR對APP的影響4 4.Cajal bodies與ANKS1B的交互作用6 5.Calpain在ANKS1B進核現象中扮演的角色7 材料與方法9 一、建構質體DNA 9 二、APP與ANKS1B交互作用的探討-共軛焦顯微鏡11 三、APP與ANKS1B交互作用的探討-抽核內蛋白13 四、鈣離子在APP與ANKS1B的交互作用中扮演的角色-流式細胞儀15 實驗結果16 1.闡明APP processing對ANKS1B進核現象的影響16 1-1 以NMDA刺激SH-SY5Y細胞株促使ANKS1B 進入細胞核中16 1-2 AICD的釋放影響ANKS1B受NMDA刺激後的進核現象16 1-3 overexpress帶有YENPTY序列的AICD會導致ANKS1B進入細胞核中17 1-4 NMDA對APP processing的影響17 2.探索ANKS1B在進入細胞核的過程中可能的調控路徑18 2-1 ANKS1B N端不需經NMDA刺激即可進入細胞核中18 2-2 AICD可能為ANKS1B 進入細胞核過程中幫助其入核的carrier 18 2-3 ANKS1B進核過程中可能幫助其斷裂的蛋白酶18 討論20 圖表23 參考文獻39 | |
| dc.language.iso | zh-TW | |
| dc.title | APP在NMDA刺激所引起的ANKS1B進核現象中扮演角色之探討 | zh_TW |
| dc.title | Investigation on the role of APP in NMDA-mediated translocation of ANKS1B | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 98-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 李財坤,兵岳忻,顧記華 | |
| dc.subject.keyword | ANKS1B, | zh_TW |
| dc.relation.page | 46 | |
| dc.rights.note | 未授權 | |
| dc.date.accepted | 2010-07-26 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 藥學研究所 | zh_TW |
| Appears in Collections: | 藥學系 | |
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