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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 吳益群(Yi-Chun Wu) | |
| dc.contributor.author | Pei-Ken Hsu | en |
| dc.contributor.author | 徐培根 | zh_TW |
| dc.date.accessioned | 2021-06-13T07:47:44Z | - |
| dc.date.available | 2005-07-30 | |
| dc.date.copyright | 2005-07-30 | |
| dc.date.issued | 2005 | |
| dc.date.submitted | 2005-07-26 | |
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/35872 | - |
| dc.description.abstract | 在多細胞生物中，正確的清除細胞自伐所造成的死亡細胞對於個體的生存十分重要。在線蟲死亡細胞的清除過程中，PSR-1被認為是作用在CED-2、CED-5、CED-10及CED-12上游的受器，調控這個過程。我們證實PSR-1會直接與CED-5及CED-12有直接的交互作用(Wang et al., 2003)，並且找出PSR-1中參與作用的區域。PSR-1中另外可能有2個NLS，所以我們產生α-GST-PSR-1-IN的多株抗體，希望能分析PSR-1在細胞內的分佈。但是沒有抗體可以辨識線蟲lysate中自源性或是過量表現的PSR-1蛋白質。我們同時也在psr-1突變種的線蟲中表現不同片段的PSR-1蛋白質(dNLS1, dNLS-2, dNLS1&2, dTM)，發現只有PSR-1-dTM不能復原psr-1突變所造成的細胞死亡清除的缺失。因此PSR-1是作用在細胞膜上來促進死亡細胞的吞噬，並且可能是扮演受器的角色。
為了了解psr-1和其他參與吞噬作用的基因之間的關係，我們觀察雙重或三重突變種中的細胞屍體數目。我們也發現了psr-1及mer-1可能共同作用在吞噬的路徑並且兩者間無直接的交互作用。另外，我們發現unc-73及mig-2可能共同作用在一個psr-1沒有參與的吞噬路徑。根據我們的實驗，我們推測PSR-1是可能扮演吞噬受器的角色來調控細胞屍體的吞噬，並且可能經由與MER-1共同作用來達成。 | zh_TW |
| dc.description.abstract | In multicellular organisms, the proper removal of apoptotic cell corpses prevents the possible dispersal of harmful cellular contents from dying cells. In C. elegans, PSR-1 is proposed to function as a receptor and act upstream of the pathway mediated by CED-2, CED-5, CED-10, and CED-12, possibly through physical interaction with CED-5 and CED-12 to control the engulfment process (Wang et al., 2003). We further mapped the binding region in PSR-1 for CED-5 and CED-12 interaction. To examine the expression pattern of PSR-1, we generated mouse and rabbit polyclonal antibodies against GST-PSR-1-IN fusion protein in order to test the subcellular localization of PSR-1. However, these antibodies and α-human PSR antibodies fail to recognize either bacterially-expressed GST-PSR-1-IN or endogenous or overexpressed PSR-1 in worm lysates. In addition to a transmembrane domain (TM), PSR-1 is predicted to possess two nuclear localization signals (NLSs). To test if any of these motifs is important for PSR-1 function, we performed deletion assays. We found that TM but not NLS is important for the engulfment function of PSR-1. These results support the previous hypothesis that PSR-1 functions on the cell membrane and possibly as a receptor to promote cell corpses uptake.
In order to investigate the relationship between psr-1 and other possible engulfment genes, mer-1, unc-73, and mig-2, we analyzed the numbers of corpse in double and triple mutants. We showed that psr-1 and another engulfment receptor, mer-1, act in the same genetic pathway, and that there is no direct interaction between PSR-1 and MER-1 intracellular or extracellular domains. Besides, unc-73 and mig-2 may play minor roles and act in the same genetic pathway which does not involve psr-1 to control cell-corpse engulfment. Together our experiments suggested that PSR-1 may act as a membrane receptor to regulate cell-corpse engulfment and that it may function with MER-1 to achieve this process. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-13T07:47:44Z (GMT). No. of bitstreams: 1 ntu-94-R92B43009-1.pdf: 14991530 bytes, checksum: 6915996728f7da3b2aac0494fb730125 (MD5) Previous issue date: 2005 | en |
| dc.description.tableofcontents | Table of Contents
Table of Contents………………………………………………………………….1 Abstract…………………………………………………………………………….4 中文摘要...........................................................................................................6 Introduction……………………………………………………………………..…7 Results……………………………………………………………………………21 PSR-1 Is a Highly Conserved Novel Protein………………………………..21 PSR-1 Interacts with CED-5 and CED-12 via Its Intracellular C-terminal Regions………………………………………………………………………….22 PSR-1 Likely Function on Cell Membrane to Promote Cell-Corpse Engulfment……………………………………………………………………...24 PSR-1-GFP and GFP-PSR-1 Localization in Cell Nuclei and Deletion of the 2nd NLS Compromised the Nuclear Localization……................................26 psr-1 and mer-1 Possibly Act in the Same Genetic Pathway to Control Cell-Corpse Engulfment……………………………………………………….27 PSR-1 and MER-1 do not Interact through Their Intracellular Domains or Extracellular Domains………………………………………………………….28 unc-73 and mig-2 Possibly Act in the Same Genetic Pathway to Regulate Cell-Corpse Clearance………………………………………………………...29 psr-1 Likely Functions in Parallel with unc-73 and mig-2 to Control Cell-Corpse Engulfment……………………………………………………….30 Polyclonal α-PSR-1-IN or α-Human PSR Antibodies Failed to Recognize either Bacterial Expressed PSR-1-IN or Endogenous PSR-1 in Worm Lysates…………………………………………………………………………..31 2 Discussion………………………………………………………………………..32 PSR Promotes the Clearance of Apoptotic Cell Corpses………………….32 PSR-PS Ligation may be a Simple Tethering Mechanism…………………33 PSR Has Vital Functions in Fundamental Developmental Processes……34 The Subcellular Localization of PSR…………………………………………35 Cell-Corpse Engulfment Signaling Involving PSR-1, MER-1, UNC-73, and MIG-2……………………………………………………………………………37 Materials and Methods………………………………………………………….39 Strains and Genetics…………………………………………………………..39 Yeast-Two-Hybrid Assay………………………………………………………39 GST Pull-Down Assay (in vitro Binding Assay)……………………………...40 Antibodies and Western Blotting……………………………………………...41 References……………………………………….………………………………..42 Figures……………………………………………………………………………52 Figure 1 Molecules and Signaling Pathways Involved in Cell Corpse Engulfment in C. elegans and Their Mammalian Homologues……………52 Figure 2 Structural Features of PSR-1 and homologues in other species…………………………………………………………………………..53 Figure 3 The Intracellular Domain of PSR-1 Interacts with CED-5 and CED-12 in Yeast Two-Hybrid Assay………………………………………….54 Figure 4 Interaction of Various PSR-1 Intracellular Fragments with CED-5A …………………………………………………………………………55 Figure 5 Interaction of Various PSR-1 Intracellular Fragments with CED-5B………………………………………………………………………….56 Figure 6 Interaction of Various PSR-1 Intracellular Fragments with CED-12………………………………………………………………………….57 Figure 7 Relative Binding Abilities of PSR-1 Intracellular Fragments and human PSR to CED-5A, CED-5B and CED-12……………………………..58 Figure 8 Rescue of Cell-Corpse Engulfment Defect of the psr-1 Mutant by 3 Expressing PSR-1, PSR-1-dNLS1, PSR-1-dNLS2, and PSR-1- dNLS1&2, but not PSR-1-dTM Protein …………………………………………………..59 Figure 9 PSR-1-GFP Expression Patterns in 1.5-fold Embryos…………61 Figure 10 PSR-1-GFP Expression Patterns in 2-fold Embryos………….62 Figure 11 PSR-1-GFP Expression Patterns in Larva……………………..63 Figure 12 GFP-PSR-1 Expression Patterns in 1.5-fold Embryos……….64 Figure 13 GFP-PSR-1 Expression Patterns in 2-fold Embryos………….65 Figure 14 GFP-PSR-1 Expression Patterns in Larva…………………….66 Figure 15 psr-1 and mer-1 Possibly Act in the Same Genetic Pathway to Control Cell-Corpse Engulfment……………………………………………...67 Figure 16 The Intracellular domain of PSR-1 and MER-1 Fail to Self-Interact or Interact with Each Other in Yeast Two-Hybrid Assay……..68 Figure 17 The Extracellular domain of MER-1 Self-Interacts but Fails to Interact with the Extracellular domain of PSR-1 in Yeast Two-Hybrid Assay……………………………………………………………………………69 Figure 18 unc-73 and mig-2 may Play Minor Roles in Cell-Corpse Engulfment and Act in the Same Genetic Pathway…………………………70 Figure 19 unc-73 Enhances Cell Corpses in psr-1 Mutant Embryos at the Comma Stage…………………………………………………………………..71 Figure 20 mig-2 does not Enhance Cell Corpses in psr-1 Mutant………72 Figure 21 unc-73; mig-2 Enhances Cell Corpses in psr-1 Mutant Embryos at the Comma Stage…………………………………………………………...73 Figure 22 Western Blotting of GST-fused PSR-1 Proteins by Polyclonal Mouse and Rabbit α-PSR-1 Antibodies……………………………………...74 Figure 23 Western Blotting of GST-fused PSR-1 Proteins by α-Human PSR Antibodies…………………………………………………………………75 Figure 24 Polyclonal Mouse α-PSR-1 Antibodies Fail to Recognize Endogenous or Overexpress PSR-1 Protein in Worm Lysates……………76 Figure 25 PSR-1 and MER-1, Two Possible Cell-Corpse Receptors, may Cooperate to Promote the Clearance of Apoptotic Cell Corpse in Worm...77 | |
| dc.language.iso | en | |
| dc.subject | 吞噬 | zh_TW |
| dc.subject | 線蟲 | zh_TW |
| dc.subject | 細胞屍體 | zh_TW |
| dc.subject | engulfment | en |
| dc.subject | psr | en |
| dc.subject | cell-corpse | en |
| dc.title | 分子與遺傳分析線蟲psr-1在細胞屍體吞噬過程中的角色 | zh_TW |
| dc.title | Molecular and Genetic Analysis of C. elegans psr-1 in the Cell-Corpse Engulfment Process | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 93-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 孟子青(Tzu-Ching Meng),黃偉邦(Wei-Pang Huang) | |
| dc.subject.keyword | 線蟲,細胞屍體,吞噬, | zh_TW |
| dc.subject.keyword | psr,cell-corpse,engulfment, | en |
| dc.relation.page | 78 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2005-07-26 | |
| dc.contributor.author-college | 生命科學院 | zh_TW |
| dc.contributor.author-dept | 分子與細胞生物學研究所 | zh_TW |
| 顯示於系所單位： | 分子與細胞生物學研究所 | |
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