研究生: |
閻映丞 Yen, Ying-Cheng |
---|---|
論文名稱: |
Dynein和dynactin在突觸囊泡運輸以及在KIF1A/UNC-104的聚集與運輸中所扮演的角色 The role of dynein and dynactin in synaptic vesicle transport and axonal KIF1A/UNC-104 clustering and motility |
指導教授: |
王歐力
Wagner, Oliver |
口試委員: |
張壯榮
詹世鵬 |
學位類別: |
碩士 Master |
系所名稱: |
生命科學暨醫學院 - 分子與細胞生物研究所 Institute of Molecular and Cellular Biology |
論文出版年: | 2011 |
畢業學年度: | 99 |
語文別: | 英文 |
論文頁數: | 76 |
中文關鍵詞: | 微管分子馬達KIF1A/UNC-104 、分子馬達dynein 、輔助蛋白dynactin 、神經軸突運輸 、秀麗隱桿線蟲 |
外文關鍵詞: | KIF1A/UNC-104, dynein, dynactin, axonal transport, C. elegans |
相關次數: | 點閱:4 下載:0 |
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神經是高度特化的極性細胞,具有樹突以及單一長軸突。許多蛋白質在神經元的細胞體中合成,並形成突觸囊泡,經由樹突以及軸突運輸至突觸。此種運輸方式須藉由分子馬達dynein以及kinesin將化學能轉換為機械能量,於神經維管上移動所完成。然而,神經細胞內運輸物的運輸機制尚未完全了解,其中一個重要的問題為運輸物的雙向運動是由何種訊息所誘發? 其中一個被廣為接受的假設是一個運輸物上結合許多分子馬達,並透過協調作用活化以及去活化這些分子馬達,或是透過拔河作用來調控此雙向運動行為。UNC-104/KIF1A是神經專一性的kinesin,負責在神經軸突維管上運輸突觸囊泡前驅物,在神經維管上能觀察到其頻繁的雙向運動。我們假設此種雙向運輸是來自dynein於另一方向的拉力,因此,在這篇研究中,我們利用秀麗隱桿線蟲觀察dynein和dynactin突變的情況下,UNC-104的運輸情形。有趣的是,我們發現當dynein突變時,UNC-104往anterograde方向的運輸不受影響,因此推測UNC-104與dynein是透過協調機制調控突觸囊泡的雙向運輸。然而,UNC-104往retrograde方向的運動長度以及持續時間在dynein heavy chain-1 (dhc-1)突變之下,有顯著地增加,推測UNC-104或是一些輔助蛋白與DHC-1有交互作用,而干擾dynein的運動。進一步比較UNC-104和synaptobrevin (SNB-1,一種突觸囊泡蛋白)的運動模式,我們推測有其他的kinesin參與突觸囊泡的運輸。另一方面,dynactin p150次單位(線蟲中為dnc-1)的突變導致UNC-104往anterograde方向的運動長度以及持續時間增加,綜合其它文獻後推測,DNC-1可能透過與UNC-104間的交互作用來調控UNC-104的運輸。最後,觀察UNC-104和SNB-1的運動模式,我們推測在突觸囊泡的運輸中,DNC-1扮演很重要的輔助角色。
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