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研究生:李敏嘉
研究生(外文):Ming-Chia Lee
論文名稱:PSR-1(PhosphatidylserineReceptor)與cMER可能共同作用於C.elegans細胞吞噬動作中擔任訊息承接之受器
論文名稱(外文):PSR-1 (Phosphatidylserine Receptor) and cMER (a receptor tyrosine kinase) potentially act together as receptors to transduce apoptotic signals during the cell-corpse engulfment in C. elegans
指導教授:吳益群
指導教授(外文):Yi-Chun Wu
學位類別:碩士
校院名稱:國立臺灣大學
系所名稱:動物學研究所
學門:生命科學學門
學類:生物學類
論文種類:學術論文
論文出版年:2002
畢業學年度:90
語文別:英文
論文頁數:52
中文關鍵詞:計畫性細胞死亡受器死細胞吞噬磷酸脢細胞骨架重組
外文關鍵詞:psr-1cmercell corpseengulfmentreceptorphosphatidylserinecytoskeletonpeceptor tyrosine kinase
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有效率的清除由計畫性細胞死亡(PCD, Program Cell Death)所產生的死細胞是免疫系統機制中極為重要的一環,此舉將可避免發炎反應以及因死細胞釋放自體抗原所引發自體免疫反應,進而降低對個體的傷害。
本篇報告針對一個在各個物種間皆具高度保守度的基因PSR (Phosphatidylserine receptor)進行功能上的探討,結果發現此一原本發現於哺乳動物巨嗜細胞上可專一辨識死細胞所釋出的PS(Phosphatidylserine)訊息的受器─ 而此一基因的相似物ps-1在線蟲的細胞吞噬作用中也扮演了類似的角色, psr-1 可在吞噬細胞作用,由於在過量表現CED-2, CED-5, CED-10, 及CED-12的情況下psr的缺失性狀可被回復,且在非活體環境下可偵測到PSR可與CED-5以及CED-12結合,因而推論PSR-1的功能應為一作用於CED-2/CrK II, CED-5/Dock180, CED-10/Rac-1,與CED-12/ELMO-1此一保守訊息傳遞路徑上游的受器。
除此之外,經實驗證實另一已被證實在哺乳動物的死細胞吞噬機制中亦扮演角色的磷酸脢受器(a receptor tyrosine kinase)─mer不但也參與在線蟲死細胞吞噬過程,而且經遺傳實驗顯示其同樣位在CED-2, CED-5, CED-10與CED-12等分子上游;再經由更進一步的雙重突變實驗認為,mer 可能與psr共同作用,接收外界的訊息以活化CED-2/CrK II, CED-5/Dock180, CED-10/Rac-1,與CED-12/ELMO-1此一保守訊息傳遞路徑,進而驅動細胞骨架重組造成吞噬動作。
Apoptosis, or programmed cell death, is considered as the most physiological mode of cell death, which is used to dispose the unwanted cells. In vivo, apoptotic cells are efficiently removed by professional or nonprofessional phagocytes, which is a process thought to be essential for tissue remodeling and the resolution of inflammation. In mammalian system, macrophage recognizes apoptotic cells by several mechanisms, including recognition of the exposed phosphatidylserine (PS).
We suggest that psr, a highly conserved phosphotidylserine receptor, not only play a role in mammalian macrophage but also function in the cell corpse engulfment in C. elegans. Cell —specific expression of psr-1(C. elegans psr homologue) indicates that psr-1 functions in engulfing cell to control cell corpse engulfment. Heat shock bypass experiments suggest that psr-1 likely acts upstream of the conserved GTPase signaling pathway mediated by CED-2/CrkII, CED-5/Dock180, CED-10/Rac1 and CED-12/ELMO-1 to control the phagocytosis of cell corpses. Furthermore, we also showed that PSR could interact physically with CED-5 and CED-12 in vitro.
In addition, we found that mer, a member of Axl/Mer/tryo3 receptor tyrosine kinase, is also important in the process of cell corpse engulfment based on the phenotype analysis of cmer (RNAi) mutants. Our genetic data showed that cmer (C. elegnas mer homologue) likely also acts upstream of ced-2, ced-5, ced-10 and ced-12. The experiments in combination with our double mutant analysis suggest that PSR-1 and cMER might act together to initiate the signaling mediated by CED-2/CrkII, CED-5/Dock180 and CED-12/ELMO-1 and results in activation CED-10/Rac-1, which in turn cause cell corpse engulfment through reorganization of cytoskeleten.

中文摘要 1
Abstract 2
Introduction
Overview of apoptosis 3
Engulfment of apoptotic cells 3
Cell corpse engulfment in C. elegans 5
Result
psr-1 encodes a transmembrane protein that is evolutionary
conserved among species 10
psr-1 is important for engulfment of cell corpses during
embryogenesis 11
psr-1 likely acts in engulfing cells to control
cell corpse engulfment 12
psr-1 likely functions upstream of ced-2, 5, 10 and ced-12 13
PSR-1 interacts with CED-5 and CED-12 in vitro 15
cmer is also important for the engulfment of cell corpses during embryogenesis 17
cmer likely acts upstream of ced-2, 5, 10 and ced-12 19
cmer may act with psr-1 in the same pathway to control
cell corpse engulfment 21
Discussion
Phagocytosis of apoptotic cells in mammalian and in C. elegans 22
The function of PSR-1 in phagocytosis 23
The function of cMER in phagocytosis 24
The conserved CED-10/Rac1 GTPase signaling mediated
CED-2/CrkII, CED-5/Dock180, CED-12/ELMO-1 in
cell corpse engulfment 25
Materials and methods 26
Reference 31
Figures and tables 37

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