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標題: | 遺傳與分子分析作用在C.elegans細胞吞噬動作及DTC遷移之訊息傳遞路徑上的基因 Molecular and genetic analysis of genes that controll cell corpse engulfment and DTC migration in the nematode Caenorhabditis elegans |
作者: | Li-chun Cheng 鄭立群 |
出版年 : | 2001 |
學位: | 碩士 |
摘要: | 計畫性細胞死亡以及細胞遷移作用是多細胞生物發育過程相當重要的現象,我利用C.elegans作為模式動物,探討一群基因如何辨認外界訊息到細胞骨架重組動作發生之間扮演訊息傳遞的角色。ced-2,ced-5,ced-10,ced-12是一群突變後同時具有吞噬障礙及DTC遷移障礙的基因,經過遺傳及分子分析後,我發現在吞噬作用裡,ced-12可能是與ced-2,ced-5同時作用在ced-10上游,以一個巨大的聚合物CED-2/CED-5/CED-12活化CED-10,我認為這個作用方式與哺乳類的CrkⅡ/DOCK180/Rac訊息傳遞具有高度保守性。mig-2是一個跟細胞遷移有關的基因,所表達的蛋白跟CED-10在序列上高度相似,單突變時不產生吞噬障礙的mig-2基因若突變在ced-2,ced-5,ced-10,ced-12突變背景之下,會造成更嚴重的吞噬障礙性狀,顯示這個基因對於細胞吞噬也有影響,作用在另一調控途徑並與ced-10扮演重複性的角色。同時,觀察DTC遷移性狀也發現mig-2可能在調控DTC遷移的功能也跟ced-10重複,並且有可能作用在ced-5訊息的下游。unc-73是一個可以調控Rac-like GTPase的GEF,對DTC遷移也有影響但是不影響吞噬作用,過度表現只含第一個DH domain的unc-73B基因在ced-12突變背景下,發現可以挽救DTC遷移障礙,由於尚未找到跟ced-10、mig-2調控有關的GEF,我認為unc-73的第一個DH domain有可能作用在ced-10上游擔任調控的角色。 Programmed cell death and cell migration are essential phenomenon in animal development. I took the advantages of C.elegans to study the relationship between ced-2,ced-5,ced-10,ced-12, four genes which play important roles in both cell corpse engulfment and distal-tip cell migration. After genetic and molecular analyses, I found that ced-12 functions in the pathway mediated by ced-2, ced-5, ced-10 but not by ced-1, ced-6, ced-7 and that CED-5 can interact with CED-10 and CED-12 in vivo. These results in combination with the finding that ced-10 acts downstream of ced-2, ced-5, and ced-12 by Reddien, Horviz, Tsai and Wu, and that CED-2, CED-5 and CED-12 can form a ternary complex suggest that the big CED-2/CED-5/CED-12 complex may be important in activation of CED-10 and conserved with mammalian CrkⅡ/DOCK180/Rac pathway which is important in cytoskeleton rearrangement. The mig-2(mu28) mutation alone does not alter the engulfment of cell corpses but indeed enhances the engulfment defect in the ced-2, ced-5, ced-10, ced-12 mutant backgrounds. This result suggests that mig-2 may play a redundant role with ced-2, ced-5, ced-10, ced-12 in the engulfment process. The enhancement in the DTC-migration defect in ced-12 mutant is also observed in the ced-2 and ced-10 mutant backgrounds but not in the ced-5 backgrounds. This result suggests that ced-5 maybe a branch point in the DTC migration path. unc-73 encodes a GEF which can catalyze the mammalian Rac1 in vitro. Overexpression of unc-73B which contains only the first DH domain can rescue the Ced-12 DTC-migration defect. These data together suggest that ced-12 may activate ced-10 through unc-73 during DTC migration. |
URI: | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/75170 |
全文授權: | 未授權 |
顯示於系所單位: | 動物學研究所 |
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