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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
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dc.contributor.advisor | 吳益群(Yi-Chun Wu) | |
dc.contributor.author | Teng-Wei Huang | en |
dc.contributor.author | 黃騰緯 | zh_TW |
dc.date.accessioned | 2021-06-14T17:23:39Z | - |
dc.date.available | 2010-07-30 | |
dc.date.copyright | 2008-07-30 | |
dc.date.issued | 2008 | |
dc.date.submitted | 2008-07-24 | |
dc.identifier.citation | Albert, M. L., J. I. Kim, et al. (2000). 'alphavbeta5 integrin recruits the CrkII-Dock180-rac1 complex for phagocytosis of apoptotic cells.' Nat Cell Biol 2(12): 899-905.
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dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/41203 | - |
dc.description.abstract | 在C. elegans中,兩條平行且部分重複的訊息傳遞途徑作用於凋亡細胞的吞噬機制中,至少有八個基因(ced-1, ced-6, ced-7, dyn-1 and ced-2, ced-5, ced-10, ced-12)參與其中。這些基因一旦發生突變,就會造成吞噬功能的缺陷,並產生存留的細胞屍體。CED-2是一個帶有SH2 domain和 SH3 domain的adapter protein,它可能會與CED-5/CED-12形成的heterodimeric guanine nucleotide exchange factor結合,共同活化CED-10(small Rac GTPase),造成細胞骨架的重組,使吞噬細胞能夠吞噬凋亡細胞。我們意外的發現ced-10(n3246) mutation顯著降低ced-5 mutants中的細胞屍體數目。在使用4D顯微攝影,分析AB cell lineage和MS cell lineage中最早的14個細胞死亡過程後,結果發現ced-10(n3246)部分抑制了ced-5 mutant中的吞噬缺陷。這些結果顯示在吞噬凋亡細胞的過程中,ced-10可能具有負向調節的作用。有趣的是,ced-10(n3246)並不會減低ced-12 single mutant或ced-12; ced-5 double mutants中的細胞屍體數目,顯示ced-10的負向調節作用需要ced-12。我們也發現ced-2(n1994)可以減少ced-10(n3246)中的細胞屍體數目,而ced-2(e1752)則否;細胞屍體數目減少的原因是吞噬缺陷受到部分抑制。這些發現意味著CED-2可能透過N-terminal SH3 domain進行對吞噬機制的抑制作用。進一步的遺傳分析顯示ced-2的負向調節作用需要ced-12而不需ced-5。總括來說,透過遺傳和性狀分析,我們的研究顯示ced-2和ced-10在細胞凋亡過程中,對吞噬機制具有先前未知的負向調節作用。 | zh_TW |
dc.description.abstract | In Caenorhabditis elegans, two partially redundant pathways containing at least eight genes (ced-1, ced-6, ced-7, dyn-1 and ced-2, ced-5, ced-10, ced-12) function in the engulfment of apoptotic cells. Mutations in any of these genes cause engulfment defects and hence result in the persistence of cell corpses. CED-2, a SH2 and SH3 containing adapter protein, may bind to the CED-5/CED-12 heterodimeric guanine nucleotide exchange factor complex to activate CED-10, a small Rac GTPase, leading to cytoskeletal reorganization during engulfment of apoptotic cells. Surprisingly, we found ced-10(n3246) significantly reduced cell corpse number in ced-5 mutants. Using four-dimensional microscopic recording, we analyzed the first 14 cell deaths in the AB and MS cell lineages and found that ced-10(n3246) partially suppressed the engulfment defect of ced-5 mutants. These results reveal a possible negative role of ced-10 in cell-corpse engulfment. Interestingly, ced-10(n3246) did not reduce cell corpse number of ced-12 single or ced-12; ced-5 double mutants, indicating that the negative role of ced-10 may require ced-12. We also found that ced-2(n1994), but not ced-2(e1752), mutation reduced cell corpse number in the ced-10(n3246) background; the reduction was caused by a partial suppression of the Ced-10 engulfment defect. These findings suggest that CED-2 may exert an inhibitory function through its N-terminal SH3 domain. Further genetic analyses showed that the negative role of ced-2 required ced-12 but not ced-5. In summary, our genetic and phenotypic analyses reveal novel roles of ced-2 and ced-10 in negative regulation of cell-corpse engulfment during programmed cell death. | en |
dc.description.provenance | Made available in DSpace on 2021-06-14T17:23:39Z (GMT). No. of bitstreams: 1 ntu-97-R94b43033-1.pdf: 1390643 bytes, checksum: 5847704ba22e6386450b475f5f1e9253 (MD5) Previous issue date: 2008 | en |
dc.description.tableofcontents | Table of contents……………………………………………………1
Introduction..............................................6 Materials and Methods....................................10 C. elegans strains, alleles and genetic analysis..........10 Analysis of embryonic cell corpses........................11 Microscopy and 4D microscopic time-lapse recording........11 Results...................................................13 ced-10 mutation reduced cell corpse number of strong ced-5 mutants during embryogenesis..............................13 ced-10(n3246) mutation partially suppressed the engulfment defects in ced-5(n1812)...................................14 The negative role of ced-10 in the ced-5(n1812) background depends on ced-12. .......................................15 ced-2(n1994) mutation reduced numbers of cell corpses in ced-10(n3246) mutant in mid-embryogenesis. ...............16 ced-2(n1994) mutation reduced the duration of cell corpses in ced-10(n3246) mutant after comma stage. ...............17 The N-SH3 domain of CED-2 may participate in a negative role on CED-10. .....18 ced-2(n1994) and ced-2(e1752) mutations did not reduce cell corpse number in ced-5(n1812) mutant. ced-2(n1994) increased cell corpse number in ced-12(k149) mutant to the level similar to that of ced-5(n1812). ...............................................19 Decrease of cell corpses in ced-10(n3246) mutant by ced-2(n1994) mutation depends on ced-12 but not ced-5. ...........................................................................20 Discussion................................................21 ced-2 and ced-10 have roles in negative regulation of cell-corpse engulfment during programmed cell death. ...............................................................................21 The short isoform of CED-10 may responsible for the negative role. ...................22 CED-2 may have a negative role different to mammalian CrkII. ...........................23 Reference................................................25 Figures and Tables........................................29 Figure 1. Protein domains and the mutation sites of CED-2, CED-5, and CED-12....................................................................................................................29 Figure 2. Protein Sequence and the mutation site of CED-10.................................31 Figure 3. ced-2, ced-5, ced-10, and ced-12 mutant stains had more embryonic cell corpses than wildtype during embryogenesis. ........................................................32 Figure 4. ced-10(n3246) mutation reduced cell corpses in ced-5 mutants through embryogenesis. .......................................................................................................33 Figure 5. Comparison of the duration of first 14 cell corpses shows that ced-10(n3246) mutation reduced the duration of cell corpses in ced-5(n1812) mutant. ....................................................................................................................34 Figure 6. ced-10(n3246) mutation did not reduce cell corpse number in ced-12(k149) mutant during embryogenesis. .........................................................35 Figure 7. ced-12(k149) mutation did not enhance the engulfment defect in ced-5(n1812) mutant. ..............................................................................................36 Figure 8. ced-12(k149) mutation prevented ced-10(n3246) mutation from decreasing the cell corpse number in ced-5(n1812) mutant. ....................................................................................................................37 Figure 9. ced-2(n1994) mutation reduced cell corpses in ced-10(n3246) mutant in mid-embryogenesis. ................................................................................................38 Figure 10. Comparison of the duration of first 14 cell corpses shows that ced-2(n1994) mutation did not reduce the duration of cell corpses in ced-10(n3246) mutant. ....................................................................................................................39 Figure 11. Comparison of the duration of cell corpses precenting at comma stage shows that ced-2(n1994) mutation reduced the duration of cell corpses in ced-10(n3246) mutant. ............................................................................................40 Figure 12. ced-2(e1752) mutation increased cell corpses in ced-10(n3246) mutant during embryogenesis. ............................................................................................41 Figure 13. ced-2(e1752) mutant had more cell corpses than ced-2(n1994) mutant during embryogenesis. ............................................................................................42 Figure 14. ced-2(n1994) and ced-2(e1752) mutations did not reduce cell corpse number in ced-5(n1812) mutant. ............................................................................43 Figure 15. ced-2(n1994) mutation increased cell corpse number in ced-12(k149) mutant to the level similar to that of ced-5(n1812). ...............................................44 Figure 16. ced-2(n1994) reduced cell corpse number in ced-10(n3246)ced-5(n1812). ..................................................................................45 Figure 17. ced-12(k149) mutation prevented ced-2(n1994) mutation from decreasing the cell corpse number in ced-10(n3246) mutant. ................................46 Figure 18. Model of the negative regulatory mechanisms of ced-2 and ced-10.....47 Figure 19. The alignment of CED-2 among homologs in different species............48 Table 1. There is no difference between death time of first 13 cell corpses in AB lineage in ced-10(n3246)ced-5(n1812) double mutant and that in ced-5(n1812) mutant. ....................................................................................................................49 Table 2. More cell corpses of the first 14 cells that die were engulfed in ced-10(n3246)ced-5(n1812) than in ced-5(n1812) before 2 fold stage. .................50 Table 3. There is no difference between death time of first 13 cell corpses in AB lineage in ced-2(n1994)ced-10(n3246) double mutant and that in ced-2(n1994) mutant. ....................................................................................................................51 Table 4. Engulfed and unengulfed cell corpses of the first 14 cells that die were both increased in ced-10(n3246)ced-2(n1994) compared with in ced-10(n3246) .........................................................................................................52 Table 5. More cell corpses presenting at comma stage in ced-2(n1994)ced-10(n3246) than those in ced-10(n3246) were engulfed before 2 fold stage. ................................................................................................................53 Appendix.........................................................................................................................54 Appendix 1. Comparison of death time of the 14 cells between eif3.k(gk126) and wild type..................................................................................................................54 Appendix 2. Comparison of cell corpse duration of the 14 cell corpses between eif3.k(gk126) and wild type.....................................................................................55 Appendix 3. Comparison of time from division to death of the 3 cells between eif3.k(gk126) and wild type.............................................................................................56 | |
dc.language.iso | en | |
dc.title | 線蟲ced-2/crkII與ced-10/rac在凋亡細胞吞噬機制中具有先前未知的負向調節作用 | zh_TW |
dc.title | ced-2/crkII and ced-10/rac have previously unassigned negative roles in engulfment of apoptotic cells in C. elegans | en |
dc.type | Thesis | |
dc.date.schoolyear | 96-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 黃偉邦(Wei-Pang Huang),陳光超(Guang-Chao Chen) | |
dc.subject.keyword | 線蟲,凋亡細胞,吞噬機制, | zh_TW |
dc.subject.keyword | ced-2,ced-10,engulfment, | en |
dc.relation.page | 56 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2008-07-26 | |
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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