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研究生:楊維康
研究生(外文):Wei-Kan Yang
論文名稱:Nak調控果蠅的樹突型態生成
論文名稱(外文):Numb-associated kinase regulates dendritic morphogenesis in Drosophila
指導教授:簡正鼎簡正鼎引用關係
指導教授(外文):Cheng-Ting Chien
學位類別:碩士
校院名稱:國立陽明大學
系所名稱:遺傳學研究所
學門:生命科學學門
學類:生物訊息學類
論文種類:學術論文
論文出版年:2004
畢業學年度:92
語文別:英文
論文頁數:69
中文關鍵詞:樹突
外文關鍵詞:Nakdendrite
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樹突本身偉大的複雜性及多樣性使得神經細胞得以接收並處理來自於感覺和前突觸的神經訊息。利用遺傳分析的研究方法,發現到一些轉錄因子和細胞骨架調控蛋白會分別在樹突神經細胞發育中之起始期的細胞命運決定以及晚期的細胞骨架結構形成扮演重要的角色。然而即便如此,到底一個細胞命運已被決定的樹狀樹突神經細胞如何能夠生長出正確的樹突分支以覆蓋此神經細胞的接收區域仍然是顯為人知的。在本篇研究中,我發現樹突的分支及生長需要細胞內胞飲作用的活性,當利用shibire突變種來封鎖住胞飲作用時,將會完全的抑制住樹突的形成。
利用降低神經細胞中numb-associated kinase (nak) 的活性顯示出調控胞飲作用將可轉而控制樹突的分支形成及延長。Nak擁有一些和胞飲作用相關的特定胺基酸序列模組,並且能夠直接和 □□Adaptin以及Numb這兩個胞飲蛋白作用。當利用雙股核醣核苷酸干擾技術來降低樹狀樹突神經細胞中nak活性時,發現到樹突分支將會減少;相反地,當nak大量表現時卻會誘使樹狀樹突神經細胞形成更多的樹突分支。而Nak與胞飲作用相關基因間的相互作用意味著nak可能是透過胞飲作用來調控樹突的形成。在此同時,Nak的激酶活性也被證實是形成樹突所必須的,這些發現暗示了Nak可能會磷酸化某種胞飲作用中的重要因子以增加胞飲作用的活性,轉而使樹突得以形成。
The great complexity and variety of dendrite morphology enables neurons receive and computate sensory and presynaptic inputs. Genetic analysis has uncovered several transcription factors and cytoskeleton-associated proteins that play important roles in the initial step of cell fate determination and the last step of forming cytoskeletal structure, respectively. However, the process of how a specified dendritic arborization (da) neuron elaborates proper dendritic branches to cover target field is still largely unknown. Here, I show that endocytosis activity is essential for dendrite branching and growth. Blocking of endocytosis in shibire mutant during dendrite development completely inhibits branching and elongation of dendrite.
numb-associated kinase (nak) contains several endocytosis interacting motifs, and was shown to associate with □-Adaptin in vivo. Using ds-RNAi strategy, loss of dendritic branches was found in nak knockdown da neurons. Conversely, overexpression of nak in da neurons increases number of dendritic branches. Moreover, the enhancement of dendritic reduction by combining one copy of □-adaptin null mutant with nak knockdown background implies the regulatory roles of nak kinase in endocytosis during dendrite formation. Whereas overexpression of numb, a protein interacting partner of Nakthat is involved in endocytosis reduces the dendritic branches in da neurons, the phenotype is opposite for nak. In addition, numb overexpression further decreases dendrite number in nak knockdown da neurons, suggesting an antagonistic role for nak. Thus, a specified da neuron may use nak and numb to regulate endocytosis activity, which in turn controls the dendritic morphogenesis.
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