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Title: | 探討線蟲(C. elegans)接受器cPSR和cMER以及找尋有關吞噬作用的tyrosine kinase接受器 Biochemical analysis of phagocytotic receptors cPSR and cMER and screen for receptor tyrosine kinases for new phagocytotic receptors in C. elegans |
Authors: | Tsung-Yang Hsu 徐綜遠 |
Publication Year : | 2003 |
Degree: | 碩士 |
Abstract: | 細胞的自然性死亡,apoptosis或programmed cell death發生於多細胞的生物體內,訊號機制啟動時會避免發炎反應的產生與自體免疫的產生,以降低對生物體的傷害。利用線蟲(Caenorhabditis. elegans)為模式動物,細胞凋亡的形態學特徵包括有:染色質濃縮(pyknosis)、細胞質濃縮、細胞形態變得不規則而且有段裂(fragmentation)、及由凋亡細胞脫落出細胞凋亡體(apoptotic body)研究細胞計劃性死亡是指活體生物中的某些特定細胞會在特定的時間與地點會進行細胞死亡,而這種細胞死亡的過程是由生物體內的基因來控制,而細胞死亡時的屍體被吞噬細胞或臨近細胞所吞噬。 在此探討於物種間為高度保守基因的phosphatiylserine receptor(PSR)與receptor tyrosine kinase, MER;以線蟲(C. elegans)基因,c-psr與c-mer為目標基因。在之前的遺傳學研究中發現,於活體內中將c-psr mutation的背景中,將已知的CED-2/CrkII、CED-5/Dock180、CED-10/Rac過量表現,其可以援救細胞吞噬作用的缺失。而在非活體的條件中,實驗發現PSR會與CED-5和CED-12結合,因此推論cPSR可能為該訊號傳遞路徑的接受器。另一高度保守基因,receptor tyrosine kinase-----cMER,其座落於吞噬細胞(phagocyte),細胞膜表面的接受器,在與c-psr突變的實驗中,發現有相同的實驗結果;推論其一樣參與相同的訊息路徑,影響吞噬作用中細胞骨架的移動。今探討PSR與MER蛋白之間是否有相互作用,而形成heterodimmer的型式;PSR的磷酸化作用產生是否受到MER的參與。另外以遺傳學方式尋找線蟲(C. elegans)體中,是否有其他新的tyrosine kinase receptor也參與細胞吞噬作用。 The apoptosis or programmed cell death is the physical mode to remove unwanted cells by specific phagocytes and non-professional phagocyte. It is to avoid inflammation and autoimmunity. When apoptosis proceed; the macrophages are recognized phosphatidylserine, which was sent to out site of membrane of apoptotic cells. In our lab research, the in vivo genetic result that c-psr mutant background will reduce cell engulfment function, but in overexpression condition; the CED-2/CrkII, CED-5/Dock180, CED-10/Rac-1 and CED-12/ELMO-1 could rescue defect phenotype. And in vitro experiments, cPSR will interaction with CED-5. Then we suggest that c-psr take part in this signal pathway to affect cell cytoskeleton morphology. And receptor tyrosine kinase, cMER, in double mutant condition also have the same result with c-psr, so it think that c-mer also regulate CED-2/CrkII, CED-5/Dock180, CED-10/Rac-1, CED-12/ELMO-1 signal pathway, affect cytoskeleton arrangement. The gold is detected psr and mer relationship, observe whether have protein-protein interaction or not; And research whether RTK receptor take part in cell engulfment mechanism or not. |
URI: | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/75408 |
Fulltext Rights: | 未授權 |
Appears in Collections: | 動物學研究所 |
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