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  1. NTU Theses and Dissertations Repository
  2. 醫學院
  3. 分子醫學研究所
請用此 Handle URI 來引用此文件: http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/8938
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dc.contributor.advisor簡正鼎
dc.contributor.authorHsien Suoen
dc.contributor.author索先zh_TW
dc.date.accessioned2021-05-20T20:04:36Z-
dc.date.available2009-09-15
dc.date.available2021-05-20T20:04:36Z-
dc.date.copyright2009-09-15
dc.date.issued2009
dc.date.submitted2009-08-17
dc.identifier.citationBielli, A., P. O. Thornqvist, et al. (2001). 'The small GTPase Rab4A interacts with the central region of cytoplasmic dynein light intermediate chain-1.' Biochem Biophys Res Commun 281(5): 1141-53.
Blanpied, T. A., D. B. Scott, et al. (2002). 'Dynamics and regulation of clathrin coats at specialized endocytic zones of dendrites and spines.' Neuron 36(3): 435-449.
Brown, T. C., S. S. Correia, et al. (2007). 'Functional compartmentalization of endosomal trafficking for the synaptic delivery of AMPA receptors during long-term potentiation.' Journal of Neuroscience 27: 13311-13315.
Brown, T. C., I. C. Tran, et al. (2005). 'NMDA receptor-dependent activation of the small GTPase Rab5 drives the removal of synaptic AMPA receptors during hippocampal LTD.' Neuron 45(1): 81-94.
Chien, C. T., S. Wang, et al. (1998). 'Numb-associated kinase interacts with the phosphotyrosine binding domain of Numb and antagonizes the function of Numb in vivo.' Mol Cell Biol 18(1): 598-607.
Conner, S. D. and S. L. Schmid (2002). 'Identification of an adaptor-associated kinase, AAK1, as a regulator of clathrin-mediated endocytosis.' J Cell Biol 156(5): 921-9.
Conner, S. D., T. Schroter, et al. (2003). 'AAK1-mediated micro2 phosphorylation is stimulated by assembled clathrin.' Traffic 4(12): 885-90.
Cooney, J. R., J. L. Hurlburt, et al. (2002). 'Endosomal Compartments Serve Multiple Hippocampal Dendritic Spines from a Widespread Rather Than a Local Store of Recycling Membrane.' J. Neurosci. 22(6): 2215-2224.
Corty, M. M., B. J. Matthews, et al. (2009). 'Molecules and mechanisms of dendrite development in Drosophila.' Development 136(7): 1049-1061.
de Renzis, S., B. Sonnichsen, et al. (2002). 'Divalent Rab effectors regulate the sub-compartmental organization and sorting of early endosomes.' Nat Cell Biol 4(2): 124-33.
Grueber, W. B., L. Y. Jan, et al. (2002). 'Tiling of the Drosophila epidermis by multidendritic sensory neurons.' Development 129(12): 2867-2878.
Hales, C. M., J. P. Vaerman, et al. (2002). 'Rab11 family interacting protein 2 associates with Myosin Vb and regulates plasma membrane recycling.' J Biol Chem 277(52): 50415-21.
Henderson, D. M. and S. D. Conner (2007). 'A novel AAK1 splice variant functions at multiple steps of the endocytic pathway.' Mol Biol Cell 18(7): 2698-706.
Horton, A. C. and M. D. Ehlers (2003). 'Dual modes of endoplasmic reticulum-to-Golgi transport in dendrites revealed by live-cell imaging.' Journal of Neuroscience 23(15): 6188-6199.
Horton, A. C., B. Racz, et al. (2005). 'Polarized secretory trafficking directs cargo for asymmetric dendrite growth and morphogenesis.' Neuron 48(5): 757-771.
Jordens, I., M. Fernandez-Borja, et al. (2001). 'The Rab7 effector protein RILP controls lysosomal transport by inducing the recruitment of dynein-dynactin motors.' Curr Biol 11(21): 1680-5.
Kennedy, M. J. and M. D. Ehlers (2006). 'Organelles and trafficking machinery for postsynaptic plasticity.' Annual Review of Neuroscience 29: 325-362.
Nakagawa, T., M. Setou, et al. (2000). 'A novel motor, KIF13A, transports mannose-6-phosphate receptor to plasma membrane through direct interaction with AP-1 complex.' Cell 103(4): 569-81.
Newpher, T. M. and M. D. Ehlers (2008). 'Glutamate receptor dynamics in dendritic microdomains.' Neuron 58(4): 472-497.
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Park, M., J. M. Salgado, et al. (2006). 'Plasticity-Induced Growth of Dendritic Spines by Exocytic Trafficking from Recycling Endosomes.' Neuron 52(5): 817-830.
Parrish, J. Z., K. Emoto, et al. (2007). 'Mechanisms that regulate establishment, maintenance, and remodeling of dendritic fields.' Annual Review of Neuroscience 30: 399-423.
Peng, Y. H., W. K. Yang, et al. (2009). 'Nak regulates Dlg basal localization in Drosophila salivary gland cells.' Biochem Biophys Res Commun 382(1): 108-13.
Satoh, D., D. Sato, et al. (2008). 'Spatial control of branching within dendritic arbors by dynein-dependent transport of Rab5-endosomes.' Nat Cell Biol 10(10): 1164-71.
Sholl, D. A. (1953). 'Dendritic organization in the neurons of the visual and motor cortices of the cat.' J Anat 87(4): 387-406.
Smythe, E. and K. R. Ayscough (2003). 'The Ark1/Prk1 family of protein kinases. Regulators of endocytosis and the actin skeleton.' EMBO Rep 4(3): 246-51.
Stone, M. C., F. Roegiers, et al. (2008). 'Microtubules Have Opposite Orientation in Axons and Dendrites of Drosophila Neurons.' Mol. Biol. Cell 19(10): 4122-4129.
Toshima, J., J. Y. Toshima, et al. (2005). 'Phosphoregulation of Arp2/3-dependent actin assembly during receptor-mediated endocytosis.' Nat Cell Biol 7(3): 246-54.
Wucherpfennig, T., M. Wilsch-Brauninger, et al. (2003). 'Role of Drosophila Rab5 during endosomal trafficking at the synapse and evoked neurotransmitter release.' J. Cell Biol. 161(3): 609-624.
Ye, B., Y. Zhang, et al. (2007). 'Growing dendrites and axons differ in their reliance on the secretory pathway.' Cell 130(4): 717-729.
Zheng, Y., J. Wildonger, et al. (2008). 'Dynein is required for polarized dendritic transport and uniform microtubule orientation in axons.' Nat Cell Biol 10(10): 1172-80.
dc.identifier.urihttp://tdr.lib.ntu.edu.tw/jspui/handle/123456789/8938-
dc.description.abstract複雜的樹突型態對於神經細胞的正常生理功能是非常重要的。儘管調控樹突發育的細胞機制尚不清楚,但最近已有研究指出外泌系統 (secretory system) 和內吞系統 (endocytic system) 扮演了重要角色。Numb-associated kinase (Nak) 是一個和內吞系統相關的磷酸激酶,並且調控樹突的型態生成。利用核酸干擾技術在果蠅樹狀神經細胞降低Nak蛋白的表現量時,會導致樹突分支減少。在過去利用融合螢光蛋白的方式,已經知道YFP-Nak會和Clathrin light chain-GFP有很好的共位現象,然而,對於Nak調控樹突發育的分子機制仍不明瞭。在本篇研究中,我檢驗象徵內吞作用不同路徑的螢光融合蛋白 (包括: Rab4mRFP, Rab5GFP, Rab11GFP及 ManIIGFP)在樹突中的數量及分布情形,發現不同的內吞胞器在樹突中會有不同且極性的分布,如: Rab4mRFP主要位在靠近神經細胞體的樹突中,然而Rab11GFP則相反,主要位在遠離細胞體的樹突內。這項結果暗示了不同的樹突區域可能需要不同的內吞系統活性。接著,我發現這些螢光蛋白在樹狀神經的樹突分支點,都和YFPNak有相當好的共位現象。然而,當我利用核酸干擾技術抑制Nak蛋白表現時,這些螢光蛋白的分布和數量都不受影響。還有,活體影像顯示YFPNak和Rab5GFP在樹突中具有不同的移動行為。總的來說,本篇研究的實驗數據顯示Nak不調控Rab4mRFP、 Rab5GFP、Rab11GFP及ManIIGFP 等內吞系統胞器蛋白的數量及極性分布之建立。zh_TW
dc.description.abstractThe great complexity of dendrites is important for their proper functions on receiving and integrating signals. Although the cellular mechanisms regulating dendrite development are largely unknown, secretory and endocytic pathways were recently shown to be involved. Numb-associated kinase (Nak) is an endocytic kinase required for dendrite morphogenesis. Nak depleted da neurons showed decreased numbers of dendritic branches. YFP-Nak is highly co-localized with clathrin light chain (Clc)-GFP at the tips of growing dendrites; however, the molecular mechanisms of Nak in dendrites are still unclear. I am interested in dissecting the endocytic steps that Nak participates in. In this study, I demonstrated the differential distribution of Rab4-mRFP, Rab5-GFP, Rab11-GFP, and ManII-GFP along the dendritic processes, in which Rab4-mRFP and Rab11-GFP preferentially distributed in proximal or distal dendrites, respectively. This data suggest the distinct requirements of cellular activities in different regions of dendrites. Although YFP-Nak colocalized largely with all the examined endocytic markers, knocked-down Nak by RNAi did not exert significant effects on the numbers and distributions of these markers. Moreover, YFP-Nak showed different dynamics with Rab5-GFP and Rab4-mRFP. Collectively, Nak is not functioning in the establishment and maintenance of the polarized distributions of Rab4-mRFP, Rab5-GFP, Rab11-GFP, and ManII-GFP.en
dc.description.provenanceMade available in DSpace on 2021-05-20T20:04:36Z (GMT). No. of bitstreams: 1
ntu-98-R96448008-1.pdf: 6883194 bytes, checksum: 23b4c60d9c6dbd037426e19aaffbd194 (MD5)
Previous issue date: 2009
en
dc.description.tableofcontentsAbstract iii
目錄 iv
圖目錄 v
Introduction 1
Results 9
Differential Occupation of Endocytic Compartments along da Dendrites 9
Colocalizations between YFPNak and Endocytic markers 14
Marker distribution in nak knock-down da dendrites 17
Dynamics of YFPNak and Endocytic Markers 20
Discussion 22
Highly enriched Rab4mRFP in proximal dendrites 22
Differential Requirements of Endocytic Machineries in Different Dendritic Regions 23
Dendritic branch points are specialized structures 25
Nak is not involved in the formations and the polar distributions of examined endocytic components 27
YFPNak puncta showed behavioral differences with endocytic markers 29
Rab endosomes and motor proteins 30
Materials and Methods 33
Drosophila strains 33
Confocal Imaging 33
Live-imaging for trafficking of endocytic markers 33
Scoring of dendritic distribution of endocytic markers 34
Measurement of colocalization 34
References 36
dc.language.isoen
dc.title果蠅神經樹突中內吞系統的分布及Nak調控zh_TW
dc.titleLocalization and Nak regulation of endocytic machineries in Drosophila da dendritesen
dc.typeThesis
dc.date.schoolyear97-2
dc.description.degree碩士
dc.contributor.oralexamcommittee吳君泰,孫以瀚
dc.subject.keywordNak,Rab4,Rab5,Rab11,內吞,樹突,果蠅,zh_TW
dc.subject.keywordNak,Rab4,Rab5,Rab11,endocytosis,dendrite,drosophila,en
dc.relation.page65
dc.rights.note同意授權(全球公開)
dc.date.accepted2009-08-17
dc.contributor.author-college醫學院zh_TW
dc.contributor.author-dept分子醫學研究所zh_TW
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