Please use this identifier to cite or link to this item:
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/32968Full metadata record
| ???org.dspace.app.webui.jsptag.ItemTag.dcfield??? | Value | Language |
|---|---|---|
| dc.contributor.advisor | 王淑美 | |
| dc.contributor.author | Yi-Jen Chen | en |
| dc.contributor.author | 陳怡珍 | zh_TW |
| dc.date.accessioned | 2021-06-13T04:20:29Z | - |
| dc.date.available | 2006-08-03 | |
| dc.date.copyright | 2006-08-03 | |
| dc.date.issued | 2006 | |
| dc.date.submitted | 2006-07-23 | |
| dc.identifier.citation | Akhand AA, Kato M, Suzuki H:Carbonyl compounds cross-link cellular proteins and activate protein-tyrosine kinase p60c-Src. J Cell Biochem. 72:1-7, 1999
Amoui M, Draber P, Draberova L:Src family-selective tyrosine kinase inhibitor, PP1, inhibits both FcεRI- and Thy-1-mediated activation of rat basophilic leukemia cells. Eur. J. Immunol 27:1881-1886, 1997 Avalos AM, Arthur WT, Schneider P, et al: Aggregation of integrins and RhoA activation are required for Thy-1-induced morphological changes in astrocytes. Journal of Biological Chemistry 279:39139-39145, 2004 Avalos AM, Labra CV, Questa AFG, et al: Signaling triggered by Thy-1 interaction with beta(3) integrin on astrocytes is an essential step towards unraveling neuronal Thy-1 function. Biological Research 35:231-238, 2002 Barker TH, Grenett HE, MacEwen MW, et al: Thy-1 regulates fibroblast focal adhesions, cytoskeletal organization and migration through modulation of p190 RhoGAP and Rho GTPase activity. Experimental Cell Research 295:488-496, 2004 Barlow JZ, Huntley GW: Developmentally regulated expression of Thy-1 in structures of the mouse sensory-motor system. Journal of Comparative Neurology 421:215-233, 2000 Barlow JZ, Kelley KA, Bozdagi O, et al: Testing the role of the cell-surface molecule Thy-1 in regeneration and plasticity of connectivity in the CNS. Neuroscience 111:837-852, 2002 Beech JN, Morris RJ, Raisman G: Density of Thy-1 on axonal membrane of different rat nerves. J Neurochem 41:411-417, 1983 Chen CH, Wang SM, Yang SH, et al: Role of Thy-1 in in vivo and in vitro neural development and regeneration of dorsal root ganglionic neurons. J Cell Biochem 94:684-694, 2005 Connor JA:Digital imaging of free calcium changes and of spatial gradients in growing processes in single, mammalian central nervous system cells. Proc. Natl. Acad. Sci. USA 83:6179-6183, 1986 Crump JG:The SAD-1 kinase regulates presynaptic vesicle clustering and axon termination. Neuron 29:115-129, 2001 Deisseroth K, Heist EK, Tsien RW:Translocation of of calmodulin to the nucleus supports CREB phosphorylation in hippocampal neurons. Nature 392:198-202, 1998 Doherty P, Singh A, Rimon G, et al: Thy-1 Antibody-Triggered Neurite Outgrowth Requires an Influx of Calcium into Neurons Via N-Type and L-Type Calcium Channels. Journal of Cell Biology 122:181-189, 1993 Doherty P, Williams G, Williams EJ: CAMs and axonal growth: a critical evaluation of the role of calcium and the MAPK cascade. Mol Cell Neurosci 16:283-295, 2000 Draberova L, Amoui M, Draber P:Thy-1-mediated activation of rat mast cells: the role of Thy-1 membrane microdomains. Immunology 87:141-148, 1996 Draberova L, Draber P:Thy-1 glycoprotein and src-like protein-tyrosine kinase p53/p56Lyn are associated in large detergent-resistant complexes in rat basophilic leukemia cells. Proc. Natl. Acad. Sci. USA 90:3611-3615, 1993 Drevot P, Langlet C, Guo XJ, et al:TCR signal initiation machinery is pre-assembled and activated in a subset of membrane rafts. EMBO J. 21:1899-908, 2002 Dreyer EB, Leifer D, Heng JE, et al:An astrocytic binding site for neuronal Thy-1 and its effect on neurite outgrowth. Proc. Natl. Acad. Sci. USA 92:11195-11199, 1995 Durrheim GA, Garnett D, Dennehy KM, et al:Thy-1 associated pp85–90 is a potential docking site for SH2 domain-containing signal transduction molecules. Cell Biol Int 25:33-42, 2001 Firer MA, Zacharia BZ, Kostikov M, et al:The Thy-1 molecule: its properties and functions, Isr. J. Med. Sci. 31:382-386, 1995 Fukuda M, Gotoh Y, Tachibana T:Induction of neurite outgrowth by MAP kinase in PC12 cells. Oncogene. 11:239-44, 1995 Ghosh A, Greenberg ME:Calcium signaling in neurons:Molecular mechanisms and cellular consequences. Science 268:239-247,1995 Goshima Y, Ohsako S, Yamauchi T: Overexpression of Ca2+/calmodulin-dependent protein kinase II in Neuro2a and NG108-15 neuroblastoma cell lines promotes neurite outgrowth and growth cone motility. J Neurosci. 13:559-67, 1993 Henke RC, Seeto GS, Jeffrey PL: Thy-1 and AvGp50 signal transduction complex in the avian nervous system: c-Fyn and G alpha i protein association and activation of signalling pathways. Journal of Neuroscience Research 49:655-670, 1997 Hueber AO, Bernard AM, Battari CL et al:Thymocytesin Thy-1-/- mice show augmented TCR signaling and impaireddifferentiation, Curr. Biol. 7:705-708, 1997 Illario M, Cavallo AL, Bayer KU: Calcium/Calmodulin-dependent Protein Kinase II Binds to Raf-1 and Modulates Integrin-stimulated ERK Activation. J. Bio. Chem. 278:45101-45108, 2003 Impey S, Obrietan K, Wong ST, et al:Cross talk between ERK and PKA is requiredfor Ca2+ stimulation of CREB-dependent transcription and ERK nuclear translocation. Neuron 21:869-883, 1998 Jeng CJ, McCarroll SA, Martin TF, et al: Thy-1 is a component common to multiple populations of synaptic vesicles. J Cell Biol 140:685-698, 1998 Jessen U, Novitskaya V, Pedersen N, et al: The transcription factors CREB and c-Fos play key roles in NCAM-mediated neuritogenesis in PC12-E2 cells. J Neurochem 79:1149-1160, 2001 Kai S, Derek T: Lipid rafts and signal transduction. Nature review 1:31-41, 2000 Kamiguchi H, Long KE, Pendergast M, et al:The neural cell adhesion molecule L1 interacts with the AP-2 adaptor and is endocytosed via the clathrinmediated pathway. J. Neurosci. 18:5311-5321, 1998 Kolkova K, Novitskaya V, Pedersen N, et al: Neural cell adhesion molecule-stimulated neurite outgrowth depends on activation of protein kinase C and the Ras-mitogen-activated protein kinase pathway. J Neurosci 20:2238-2246, 2000 Kroczek RA, Gunter KC, Germain RN, et al:Thy-1 functions as a signal transduction molecule in T lymphocytes and transfected B lymphocytes. Nature 322:181-184, 1986 Lancki DW, Qian D, Fields P, et al:Differential requirement for protein tyrosine kinase Fyn in the functional activation of antigen-specific T lymphocyte clones through the TCR or Thy-1. J. Immunol. 154:4363-4370, 1995 Lawrence R, Kai S: Lipid rafts and membrane dynamics. J. Cell Science 118: 1099-1102, 2005 Leifer D, Dreyer EB, Lipton SA:Immunofluorescent characterization of retinal ganglion cell neurites cultured on substrates coated with antibodies against Thy-1. Exp Neurol. 113:386-90, 1991 Leifer D, Lipton SA, Barnstable CJ, et al: Monoclonal antibody to Thy-1 enhances regeneration of processes by rat retinal ganglion cells in culture. Science 224:303-306, 1984 Leyton L, Quest AF, Bron C:Thy-1/CD3 coengagement promotes TCR signaling and enhances particularly tyrosine phosphorylation of the raft molecule. LAT. Mol. Immunol 36:755, 1999 Leyton L, Schneider P, Labra CV, et al: Thy-1 binds to integrin beta(3) on astrocytes and triggers formation of focal contact sites. Current Biology 11:1028-1038, 2001 Lipton SA, Leifer D, Barnstable CJ: Selectivity of Thy-1 Monoclonal-Antibodies in Enhancing Neurite Outgrowth. Neuroscience Letters 137:75-77, 1992 Lipton SA, Leifer D, Barnstable CJ: Selectivity of Thy-1 Monoclonal-Antibodies in Enhancing Neurite Outgrowth. Neuroscience Letters 137:75-77, 1992 Loberto N, Prioni S, Bettiga A:The membrane environment of endogenous cellular prion protein in primary rat cerebellar neurons. J Neurochem. 95:771-83, 2005 Loers G, Chen S, Grumet M, et al: Signal transduction pathways implicated in neural recognition molecule L1 triggered neuroprotection and neuritogenesis. J. Neurochemistry 92:1463-1476, 2005 Lonze BE, Ginty DD:Function and regulation of CREB family transcription factors in the nervous system. Neuron 35:605-623, 2002 Low MG, Kincade PW: Phosphatidylinositol is the membrane-anchoring domain of the Thy-1 glycoprotein. Nature 318:62-64, 1985 Lucero HA, Robbins PW: Lipid rafts-protein association and the regulation of protein activity. Archives of Biochemistry and Biophysics 426:208-224, 2004 Mahanthappa NK, Patterson PH: Thy-1 Involvement in Neurite Outgrowth - Perturbation by Antibodies, Phospholipase-C, and Mutation. Developmental Biology 150:47-59, 1992 Mansour Haeryfar SM and Hoskin DW: Thy-1：More than a Mouse Pan-T Cell Marker. The Journal of Immunology 173:3581-3588, 2004 Mao Z, Bonni A, Xia F, et al:Neuronal activity-dependent cell survival mediated by transcription factor MEF2. Science 286:785-790, 1999 Messer A, Snodgrass GL, Maskin P: Enhanced survival of cultured cerebellar Purkinje cells by plating on antibody to Thy-1. Cell Mol Neurobiol. 4:285-90,1984 Morris R: Thy-1 in developing nervous tissue. Developmental Neuroscience 7:133-160, 1985 Morris R: Thy-1, the enigmatic extrovert on the neuronal surface. Bioessays 14:715-722, 1992 Narisawa-Saito M, Yamanashi Y, Morioka T, et al: Thy-1 molecule associates with protein tyrosine kinase(s) in rat mesangial cells. Clin Exp Immunol 106:86-90, 1996 Ngan V, Matthew EK, Olga V, et al: A cAMP-response element binding protein-induced microRNA regulates neuronal morphogenesis. PANS 102: 16426-16431, 2005 NostenBertrand M, Errington ML, Murphy K, et al: Normal spatial learning despite regional inhibition of LTP in mice lacking Thy-1. Nature 379:826-829, 1996 Obata K, Yamanaka H, Dai Y, et al:Differential activation of MAPK in injured and uninjured DRG neurons following chronic constriction injury of the sciatic nerve in rats. European Journal of Neuroscience 20: 2881-2895, 2004 Robinson MJ, Stippee SA, Goldsmith E, et al:A constitutively active and nuclear form of the MAP kinase ERK2 is sufficient for neurite outgrowth and cell transformation. Curr. Biol. 8:1141-1150, 1998. Saleh M, Lang RJ, Bartlett PF:Thy-1-mediated regulation of a low-threshold transient calcium current in cultured sensory neurons. Proc. Natl. Acad. Sci. USA 85:4543-4547, 1988 Schaefer AW, Kamei Y, Kamiguchi H:L1 endocytosis is controlled by a phosphorylation-dephosphorylation cycle stimulated by outside-in signaling by L1. J. Cell Biol. 157:1223-1232, 2002 Schmid RS, Graff RD, Schaller MD, et al: NCAM stimulates the Ras-MAPK pathway and CREB phosphorylation in neuronal cells. J Neurobiol 38:542-558, 1999 Schmid RS, Pruitt WM, Maness PF:A MAP kinasesignaling pathway mediates neurite outgrowth on L1 and requires Src-dependent endocytosis. J. Neurosci. 20:4177-4188, 2000 Shenoy-Scaria AM, Kwong J, Fujita T, et al:Interaction of glycosyl-phosphatidylinositol anchor and protein tyrosine kinases p56Lck and p59Fyn 1. J. Immunol. 149:3535-3541, 1992 Simons K, Toomre D:Lipid rafts and signal transduction. Nat. Rev. Mol. Cell Biol. 1:31-39.2000 Stefanova I, Horejsi V, Ansotegui IJ, et al: GPI-anchored cell-surface molecules complexed to protein tyrosine kinases. Science 254:1016-1019, 1991 Stemple DL, Mahanthappa NK, Anderson DJ: Basic FGF induces neuronal differentiation, cell division, and NGF dependence in chromaffin cells: a sequence of events in sympathetic development. Neuron 1:517-25,1988 StuermerCA, Lang DM, Kirsch F, et al:Glycosylphosphatidyl inositol-anchored proteins and Fyn kinase assemble in noncaveolar plasma membrane microdomains defined by reggie-1 and-2. Mol. Biol. Cell 12:3031-3045, 2001 Sunyach C, Jen A, Deng J, et al: The mechanism of internalization of glycosylphosphatidylinositol-anchored prion protein. EMBO J. 22:3591-3601, 2003 Surviladze Z, Draberova L, Kovarova M, et al:Differential sensitivity to acute cholesterol lowering of activationmediated via the high-affinity IgE receptor and Thy-1 glycoprotein. Eur. J. Immunol 31:1-10, 2001 Thomas PM, Samelson LE: The glycophosphatidylinositol-anchored Thy-1 molecule interacts with the p60Fyn protein tyrosine kinase in T cells. J Biol Chem 267:12317-12322, 1992 Tiveron MC, Barboni E, Rivero FBP, et al: Selective-Inhibition of Neurite Outgrowth on Mature Astrocytes by Thy-1 Glycoprotein. Nature 355:745-748, 1992 Tiveron MC, Nosten-Bertrand M, Jani H, et al: The mode of anchorage to the cell surface determines both the function and the membrane location of Thy-1 glycoprotein. Journal of Cell Science 107:1783-1796, 1994 Tojima T, Ito E:Signal transduction cascades underlying de novo protein synthesis required for neuronal morphogenesis in differentiating neurons. Prog. in Neurobiology 72:183-193, 2004 Tojima T, Kobayashi S, Ito E: Dual role of cyclic AMP-dependent protein kinase in neuritogenesis and synaptogenesis during neuronal differentiation. J. Neurosci. Res. 74:829-837, 2003a. Tojima T, Yamane Y, Takagi H, et al:Three-dimensional characterization of interior structure of exocytotic apertures of nerve cells using atomic force microscopy. Neuroscience 101: 471-481, 2000a Xue GP, Rivero BP, Morris RJ: The surface glycoprotein Thy-1 is excluded from growing axons during development: a study of the expression of Thy-1 during axogenesis in hippocampus and hindbrain. Development 112:161-176, 1991 | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/32968 | - |
| dc.description.abstract | Thy-1又稱CD90，是一種位於非囊泡性脂筏（non-caveolar lipid raft microdomains）的小型表面醣蛋白，與Src家族激酶有高度的關連性，主要出現在胸腺細胞、T淋巴球及神經細胞等細胞膜上，並呈現點狀的分佈。過去學者們的研究支持，Thy-1對於神經胞突生長扮演了抑制的角色，若干擾膜上Thy-1的功能，的確能促使視網膜神經元及PC12神經瘤母細胞胞突的生長、維持及再生。首先，我們想了解以Thy-1抗體阻斷背根神經元膜上Thy-1之正常功能，是否能促使其胞突生長？接著，Thy-1與抗體結合後，活化了哪些訊息路徑進而影響胞突生長？而這些訊息路徑的傳遞是否與脂筏（lipid rafts）有關？
我們在培養兩天的背根神經元，進行相關的實驗。我們發現，以Thy-1抗體處理六小時後，無論是大型或小型背根神經元，神經胞突長度及其分枝複雜程度均明顯增加。若以methyl-beta-cyclodextrin（MbCD）破壞脂筏（lipid rafts）的結構後，則抑制了Thy-1抗體所誘導的胞突生長，證明Thy-1抗體須經由神經細胞膜上完整且功能正常的脂筏才能達到其作用。而在此過程中，Thy-1抗體除了會導致Thy-1產生內質化（internalization）的情形，可能也趨使了與Thy-1連結的Src家族激酶之訊息活化。於是我們以西方墨點分析來證明，Thy-1抗體處理0、15、30及60分鐘後，的確能使得c-Src、MEK1/2、CaMKII、VASP（PKA受質）及CREB的磷酸化表現增加。接著分別使用MEK的抑制劑PD98059、CaMKII的抑制劑KN-93及PKA的抑制劑Protein kinase inhibitor（PKI）預先處理30分鐘，再加入Thy-1抗體處理六小時後，均可抑制大型及小型背根神經元的胞突生長。進一步以PP2抑制Src活化，可抑制Thy-1抗體處理所引起的MEK磷酸化，足見Src為MEK的上游調控分子。除此之外，實驗也証明以Thy-1抗體處理後，活化了MEK及PKA，進而造成CREB的磷酸化。根據學者們的研究，CREB磷酸化可以促進與胞突生長有關的基因，如neurofilament light chain subunit（NF-L）、brain-derived neurotrophic factor（BDNF）及nerve growth factor（NGF）等表現。所以，我們推論Thy-1抗體的作用，可能經由Thy-1-enriched microdomains，啟動和Thy-1結合的c-Src激酶，進行一連串的訊息傳導：c-Src-MEK-ERK-CREB-neurite outgrowth，同時也有可能活化了PKA-CREB，CaMKII及其下游標的分子，而造成胞突生長的反應。 | zh_TW |
| dc.description.abstract | Thy-1 (CD90), a glycosylphosphatidylinositol (GPI) protein, is located at non-caveolar lipid raft and often colocalized with Src-family kinases within these domains, and is expressed mainly in thymus epithelial cells, T-lymphocytes and neurons. Previous studies suggest an inhibitory role of Thy-1 in neurite growth in retinal ganglion neurons and neuroblastoma cell lines. Using cultured dorsal root ganglion (DRG) neurons, we investigated the underlying signaling mechanism responsible for the effect of Thy-1 antibody on promoting neurite outgrowth. Thy-1 was enriched in microdomain-like punctates on the cell membrane by immunofluorescence observation. Treatment with Thy-1 antibody stimulated neurite outgrowth and increased branching complexity of the neurites in both small and large neurons. This effect of Thy-1 antibody was dependent on the integrity of Thy-1-enriched microdomains, since disruption of these domains by methyl-beta-cyclodextrin (MbCD) prevented Thy-1 antibody-induced neurite outgrowth. Possibly via binding to membranous Thy-1, Thy-1 antibodies induced internalization of Thy-1 molecules, followed by triggering subsequent signaling involving activation of Src kinases. This transient activation of c-Src kinase resulted in increased phosphorylation of mitogen activated kinase kinase (MEK) and cyclic AMP response-element binding protein (CREB), since pretreatment with PP2 abolished Thy-1 antibody-induced neurite outgrowth in DRG neurons and the phosphorylation of MEK and CREB. Phosphorylation of CREB may guide to upregulation of some neurite outgrowth-related proteins, such as neurofilament light chain subunit (NF-L), brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF), as reported in other neuronal cells. We conclude that Thy-1 antibody activates c-Src kinase-MEK -CREB by targeting on Thy-1-enriched microdomains in the cell membrane of DRG neuron. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-13T04:20:29Z (GMT). No. of bitstreams: 1 ntu-95-R93446005-1.pdf: 13749297 bytes, checksum: 76726c20135334d602ee455455622bba (MD5) Previous issue date: 2006 | en |
| dc.description.tableofcontents | 目錄
中文摘要 ……………………………………… P.1∼P.2 英文摘要 ……………………………………… P.3∼P.4 前言 …………………………………………… P.5∼P.11 材料與方法 …………………………………… P.12∼P.21 結果 …………………………………………… P.22∼P.31 討論 …………………………………………… P.32∼P.38 參考文獻 ……………………………………… P.39∼P.48 圖片與圖片說明 ……………………………… P.49∼P.63 模式圖 ………………………………………………… P.64 | |
| dc.language.iso | zh-TW | |
| dc.title | Thy-1抗體導致大鼠背根神經元胞突生長之訊息傳遞機制探討 | zh_TW |
| dc.title | Signaling mechanisms for Thy-1 antibody-induced neurite outgrowth in dorsal root ganglionic neurons | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 94-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 謝松蒼,鄭瓊娟 | |
| dc.subject.keyword | 背根神經元,胞突生長,訊息傳遞,脂筏, | zh_TW |
| dc.subject.keyword | Thy-1,CD90,Thy-1 antibody,dorsal root ganglion,neuritogenesis,neurite outgrowth,lipid raft,signaling mechanism,Src,MEK,CaMKII,PKA,CREB, | en |
| dc.relation.page | 64 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2006-07-24 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 解剖學研究所 | zh_TW |
| Appears in Collections: | 解剖學暨細胞生物學科所 | |
Files in This Item:
| File | Size | Format | |
|---|---|---|---|
| ntu-95-1.pdf Restricted Access | 13.43 MB | Adobe PDF |
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.