研究生: |
高秀華 Hsiu-Hau Kao |
---|---|
論文名稱: |
探討Abl, Abi, FAK的果蠅突變株對於果蠅幼蟲神經肌肉聯會系統突觸產生的影響 Mutation of Drosophila Abl, Abi, or FAK alters synaptic efficacy in larval neuromuscular junction |
指導教授: |
葉世榮
Shin- Rung Yeh |
口試委員: | |
學位類別: |
碩士 Master |
系所名稱: |
生命科學暨醫學院 - 分子醫學研究所 Institute of Molecular Medicine |
論文出版年: | 2008 |
畢業學年度: | 96 |
語文別: | 中文 |
論文頁數: | 36 |
中文關鍵詞: | 神經肌肉聯會系統 、肌動蛋白 、突觸 、果蠅幼蟲 |
相關次數: | 點閱:2 下載:0 |
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肌動蛋白佔了整個細胞很大的比例,並且各種細胞中許多生理機能都是透過調控肌動蛋白來做調節。在過去,肌動蛋白大量被用來研究非神經細胞的移動、分化或是蛋白質的運輸等等,但在神經細胞上著墨甚少。由於神經細胞也跟一般細胞一樣含有許多肌動蛋白,於是有人推測肌動蛋白在神經細胞中應該也扮演著重要的角色,之後便陸陸續續有研究集中投入這塊領域,掀開調控肌動蛋白對神經系統影響的序幕。
為了窺探調控肌動蛋白對神經細胞可能造成的影響,在本篇實驗中,我們檢測了多個與調控肌動蛋白相關蛋白質的果蠅突變株:Abl1/Abl4, abiKO/abiP2, Abl1 abiKO/Abl4 abiP2, and Fak56KG00304,藉由觀察這些突變株神經肌肉聯會系統與野生型的差異,進而推估出這些蛋白質在神經細胞中可能的功能。我們根據被突變基因之間的關聯性,將果蠅突變株分成Abl組以及FAK組,分別觀察了:突觸傳送訊息的效能(synaptic transmission)、突觸小泡運輸釋放與回收的機制、突觸的可塑性是否有受到影響。結果發現在Abl組以及FAK組突觸傳送訊息的效能都有受到影響;而abi-/-以及Fak56突變株則些微影響了突觸小泡的運輸;在突觸可塑性的方面則只有abi-/-突變株有受到影響。整體的結果顯示Abl組可能參與維持突觸的強度及控制其分支的程度,而FAK可能也與控管突觸末端的生長有關。此外,較特別的是Abi可能另外參與了和cAMP cascade相關的路徑,因此可能也和學習與記憶相關。
Actin is the most abundant protein in many cells, and regulating actin seems to be an important way to modulate cell activity. Actin had drawn a lot of attention on its involvement in motility, morphogenesis and proliferation of non-neuron cells, but little in neurons. Since neuronal cells contain as much of actin as non-neuron cells, some researchers suggested that actin may also play an important role in neurons. So more and more researches invested in this field, continually.
In order to investigate the effects in which regulating actin may result in neurons, we examined some mutants about actin-interacted proteins of Drosophila larvae in this study. These mutants are Abl1/Abl4, abiKO/abiP2, Abl1 abiKO/Abl4 abiP2, and Fak56KG00304. To find the original function of these mutated protein in neurons, we observed the differences between wild-type and mutants in Drosophila Neuromuscular junction (NMJ) system. We compared many properties of Drosophila larvae which are separated into two groups, Abl and FAK, based on the relationship between these mutants. These properties are Synaptic transmission, Synaptic vesicles translocation and recycling, and Synaptic plasticity. We found that synaptic transmissions are affected both in Abl and FAK group. Besides, abi-/-and Fak56 have some effects on synaptic vesicles translocation. Furthermore, only abi-/- has effects on synaptic plasticity. Overall results implicate that Abl group may get involved in maintaining synaptic strength and controlling the extent of synaptic branch, and FAK may also get involve in control of axonal growth. In addition, Abi may have a little bit interaction with cAMP cascade which may be related with leaning and memory.
Agochiya M, Brunton VG, Owens DW, Parkinson EK, Paraskeva C, Keith WN, Frame MC. 1999. Increased dosage and amplification of the focal adhesion kinase gene in human cancer cells. Oncogene 18(41):5646-5653.
Anderson EFaCL. 1981. Stimulation-induced changes in dimensions of stalks of dendritic spines in the dentate molecular layer Experimental neurology 74(2):621-627.
Bramham CR, Srebro B. 1987. Induction of long-term depression and potentiation by low- and high-frequency stimulation in the dentate area of the anesthetized rat: magnitude, time course and EEG. Brain research 405(1):100-107.
Burgaya F, Toutant M, Studler J-M, Costa A, Le Bert M, Gelman M, Girault J-A. 1997. Alternatively Spliced Focal Adhesion Kinase in Rat Brain with Increased Autophosphorylation Activity. J Biol Chem 272(45):28720-28725.
Carballido-Lopez R. 2006. The Bacterial Actin-Like Cytoskeleton. Microbiol Mol Biol Rev 70(4):888-909.
Contestabile A, Bonanomi D, Burgaya F, Girault JA, Valtorta F. 2003. Localization of focal adhesion kinase isoforms in cells of the central nervous system. Int J Dev Neurosci 21(2):83-93.
Courtney KD, Grove M, Vandongen H, Vandongen A, LaMantia AS, Pendergast AM. 2000. Localization and phosphorylation of Abl-interactor proteins, Abi-1 and Abi-2, in the developing nervous system. Molecular and cellular neurosciences 16(3):244-257.
Cowan CA, Henkemeyer M. 2001. The SH2/SH3 adaptor Grb4 transduces B-ephrin reverse signals. Nature 413(6852):174.
Davis GW, Goodman CS. 1998. Synapse-specific control of synaptic efficacy at the terminals of a single neuron. Nature 392(6671):82.
De Camilli P, Benfenati F, Valtorta F, Greengard P. 1990. The synapsins. Annual review of cell biology 6:433-460.
Dillon C, Goda Y. 2005. The actin cytoskeleton: integrating form and function at the synapse. Annual review of neuroscience 28:25-55.
Doussau F, Augustine GJ. 2000. The actin cytoskeleton and neurotransmitter release: an overview. Biochimie 82(4):353-363.
Dunaevsky A, Blazeski R, Yuste R, Mason C. 2001. Spine motility with synaptic contact. Nat Neurosci 4(7):685-686.
Dunaevsky A, Tashiro A, Majewska A, Mason C, Yuste R. 1999. Developmental regulation of spine motility in the mammalian central nervous system. Proceedings of the National Academy of Sciences 96(23):13438-13443.
Fan P-D, Goff SP. 2000. Abl Interactor 1 Binds to Sos and Inhibits Epidermal Growth Factor- and v-Abl-Induced Activation of Extracellular Signal-Regulated Kinases. Mol Cell Biol 20(20):7591-7601.
Feng Y, Ueda A, Wu C-F. 2004. A MODIFIED MINIMAL HEMOLYMPH-LIKE SOLUTION, HL3.1, FOR PHYSIOLOGICAL RECORDINGS AT THE NEUROMUSCULAR JUNCTIONS OF NORMAL AND MUTANT <i>DROSOPHILA</i> LARVAE. Journal of Neurogenetics 18(2):377 - 402.
Fifková E VHA. 1977. Long-lasting morphological changes in dendritic spines of dentate granular cells following stimulation of the entorhinal area. J Neurocytol 6(2):211-230.
Fifkova E, Delay RJ. 1982. Cytoplasmic actin in neuronal processes as a possible mediator of synaptic plasticity. The Journal of cell biology 95(1):345-350.
Fischer M, Kaech S, Knutti D, Matus A. 1998. Rapid actin-based plasticity in dendritic spines. Neuron 20(5):847-854.
Furukawa K, Smith-Swintosky VL, Mattson MP. 1995. Evidence that actin depolymerization protects hippocampal neurons against excitotoxicity by stabilizing [Ca2+]i. Experimental neurology 133(2):153-163.
Grabbe C, Zervas CG, Hunter T, Brown NH, Palmer RH. 2004. Focal adhesion kinase is not required for integrin function or viability in Drosophila. Development (Cambridge, England) 131(23):5795-5805.
Grant SG, Karl KA, Kiebler MA, Kandel ER. 1995. Focal adhesion kinase in the brain: novel subcellular localization and specific regulation by Fyn tyrosine kinase in mutant mice. Genes Dev 9(15):1909-1921.
Grove M, Demyanenko G, Echarri A, Zipfel PA, Quiroz ME, Rodriguiz RM, Playford M, Martensen SA, Robinson MR, Wetsel WC, Maness PF, Pendergast AM. 2004. ABI2-deficient mice exhibit defective cell migration, aberrant dendritic spine morphogenesis, and deficits in learning and memory. Molecular and cellular biology 24(24):10905-10922.
Guan JL, Shalloway D. 1992. Regulation of focal adhesion-associated protein tyrosine kinase by both cellular adhesion and oncogenic transformation. Nature 358(6388):690-692.
Hooper JE. 1986. Homeotic gene function in the muscles of Drosophila larvae. The EMBO journal 5(9):2321-2329.
Hsia DA, Mitra SK, Hauck CR, Streblow DN, Nelson JA, Ilic D, Huang S, Li E, Nemerow GR, Leng J, Spencer KS, Cheresh DA, Schlaepfer DD. 2003. Differential regulation of cell motility and invasion by FAK. The Journal of cell biology 160(5):753-767.
Huang C-H, Lin T-Y, Pan R-L, Juang J-L. 2007. The Involvement of Abl and PTP61F in the Regulation of Abi Protein Localization and Stability and Lamella Formation in Drosophila S2 Cells. J Biol Chem 282(44):32442-32452.
Jan LY, Jan YN. 1976. Properties of the larval neuromuscular junction in Drosophila melanogaster. J Physiol 262(1):189-214.
Johnson BD, Byerly L. 1993. A cytoskeletal mechanism for Ca2+ channel metabolic dependence and inactivation by intracellular Ca2+. Neuron 10(5):797-804.
Jones SB, Lu HY, Lu Q. 2004. Abl tyrosine kinase promotes dendrogenesis by inducing actin cytoskeletal rearrangements in cooperation with Rho family small GTPases in hippocampal neurons. J Neurosci 24(39):8510-8521.
Juang JL, Hoffmann FM. 1999. Drosophila abelson interacting protein (dAbi) is a positive regulator of abelson tyrosine kinase activity. Oncogene 18(37):5138-5147.
Kim CH, Lisman JE. 1999. A role of actin filament in synaptic transmission and long-term potentiation. J Neurosci 19(11):4314-4324.
Koh T-W, Korolchuk VI, Wairkar YP, Jiao W, Evergren E, Pan H, Zhou Y, Venken KJT, Shupliakov O, Robinson IM, O'Kane CJ, Bellen HJ. 2007. Eps15 and Dap160 control synaptic vesicle membrane retrieval and synapse development. J Cell Biol 178(2):309-322.
Koleske AJ, Gifford AM, Scott ML, Nee M, Bronson RT, Miczek KA, Baltimore D. 1998. Essential roles for the Abl and Arg tyrosine kinases in neurulation. Neuron 21(6):1259-1272.
Korkotian E, Segal M. 2001. Spike-associated fast contraction of dendritic spines in cultured hippocampal neurons. Neuron 30(3):751-758.
Kuromi H, Kidokoro Y. 2003. Two synaptic vesicle pools, vesicle recruitment and replenishment of pools at the Drosophila neuromuscular junction. Journal of neurocytology 32(5-8):551-565.
Kuromi H, Kidokoro Y. 2005. Exocytosis and endocytosis of synaptic vesicles and functional roles of vesicle pools: lessons from the Drosophila neuromuscular junction. Neuroscientist 11(2):138-147.
Lee Y-T. 2007. Interval between burst of stimuli modulate synaptic plasticity in neuromuscular junction of Drosophila melanogaster larvae: 國立清華大學. 34 p.
Leng Y, Zhang J, Badour K, Arpaia E, Freeman S, Cheung P, Siu M, Siminovitch K. 2005. Abelson-interactor-1 promotes WAVE2 membrane translocation and Abelson-mediated tyrosine phosphorylation required for WAVE2 activation. Proceedings of the National Academy of Sciences of the United States of America 102(4):1098-1103.
Lin CH, Thompson CA, Forscher P. 1994. Cytoskeletal reorganization underlying growth cone motility. Current opinion in neurobiology 4(5):640-647.
llic D, Furuta Y, Kanazawa S, Takeda N, Sobue K, Nakatsuji N, Nomura S, Fujimoto J, Okada M, Yamamoto T, AizawaShinichi. 1995. Reduced cell motility and enhanced focal adhesion contact formation in cells from FAK-deficient mice. Nature 377(6549):539-544.
Maruoka ND, Steele DF, Au BP, Dan P, Zhang X, Moore ED, Fedida D. 2000. alpha-actinin-2 couples to cardiac Kv1.5 channels, regulating current density and channel localization in HEK cells. FEBS letters 473(2):188-194.
Matsuzaki M, Honkura N, Ellis-Davies GC, Kasai H. 2004. Structural basis of long-term potentiation in single dendritic spines. Nature 429(6993):761-766.
Mons N, Guillou JL, Jaffard R. 1999. The role of Ca2+/calmodulin-stimulable adenylyl cyclases as molecular coincidence detectors in memory formation. Cell Mol Life Sci 55(4):525-533.
Morales M, Colicos MA, Goda Y. 2000. Actin-dependent regulation of neurotransmitter release at central synapses. Neuron 27(3):539-550.
Moresco EM, Koleske AJ. 2003. Regulation of neuronal morphogenesis and synaptic function by Abl family kinases. Current opinion in neurobiology 13(5):535-544.
Moresco EM, Scheetz AJ, Bornmann WG, Koleske AJ, Fitzsimonds RM. 2003. Abl family nonreceptor tyrosine kinases modulate short-term synaptic plasticity. J Neurophysiol 89(3):1678-1687.
Nanninga N. 2001. Cytokinesis in prokaryotes and eukaryotes: common principles and different solutions. Microbiol Mol Biol Rev 65(2):319-333 ; third page, table of contents.
Newton H. Woo SNDTAPVN. 2003. Temporal spacing of synaptic stimulation critically modulates the dependence of LTP on cyclic AMP-dependent protein kinase. Hippocampus 13(2):293-300.
Puszkin S SW. 1979. The role of cytoskeleton in neuron activity. Methods Achiev Exp Pathol 9:87-111.
Qualmann B, Boeckers TM, Jeromin M, Gundelfinger ED, Kessels MM. 2004. Linkage of the actin cytoskeleton to the postsynaptic density via direct interactions of Abp1 with the ProSAP/Shank family. J Neurosci 24(10):2481-2495.
Renger JJ, Ueda A, Atwood HL, Govind CK, Wu CF. 2000. Role of cAMP cascade in synaptic stability and plasticity: ultrastructural and physiological analyses of individual synaptic boutons in Drosophila memory mutants. J Neurosci 20(11):3980-3992.
Scharf MT, Woo NH, Lattal KM, Young JZ, Nguyen PV, Abel T. 2002. Protein Synthesis Is Required for the Enhancement of Long-Term Potentiation and Long-Term Memory by Spaced Training. J Neurophysiol 87(6):2770-2777.
Shen L, Liang F, Walensky LD, Huganir RL. 2000. Regulation of AMPA receptor GluR1 subunit surface expression by a 4. 1N-linked actin cytoskeletal association. J Neurosci 20(21):7932-7940.
Shi Y, Alin K, Goff SP. 1995. Abl-interactor-1, a novel SH3 protein binding to the carboxy-terminal portion of the Abl protein, suppresses v-abl transforming activity. Genes Dev 9(21):2583-2597.
Song JK, Giniger E, Desai CJ. 2008. The receptor protein tyrosine phosphatase PTP69D antagonizes Abl tyrosine kinase to guide axons in Drosophila. Mechanisms of development 125(3-4):247-256.
van den Ent F, Amos LA, Lowe J. 2001. Prokaryotic origin of the actin cytoskeleton. Nature 413(6851):39-44.
Van Etten RA, Jackson PK, Baltimore D, Sanders MC, Matsudaira PT, Janmey PA. 1994. The COOH terminus of the c-Abl tyrosine kinase contains distinct F- and G-actin binding domains with bundling activity. The Journal of cell biology 124(3):325-340.
Westphal RS, Soderling SH, Alto NM, Langeberg LK, Scott JD. 2000. Scar/WAVE-1, a Wiskott-Aldrich syndrome protein, assembles an actin-associated multi-kinase scaffold. The EMBO journal 19(17):4589-4600.
Wills Z, Emerson M, Rusch J, Bikoff J, Baum B, Perrimon N, Van Vactor D. 2002. A Drosophila homolog of cyclase-associated proteins collaborates with the Abl tyrosine kinase to control midline axon pathfinding. Neuron 36(4):611-622.
Wills Z, Marr L, Zinn K, Goodman CS, Van Vactor D. 1999. Profilin and the Abl tyrosine kinase are required for motor axon outgrowth in the Drosophila embryo. Neuron 22(2):291-299.
Wu H, Nash JE, Zamorano P, Garner CC. 2002. Interaction of SAP97 with minus-end-directed actin motor myosin VI. Implications for AMPA receptor trafficking. The Journal of biological chemistry 277(34):30928-30934.
Yan W, Bentley B, Shao R. 2008. Distinct Angiogenic Mediators Are Required for Basic Fibroblast Growth Factor- and Vascular Endothelial Growth Factor-induced Angiogenesis: The Role of Cytoplasmic Tyrosine Kinase c-Abl in Tumor Angiogenesis. Molecular biology of the cell 19(5):2278-2288.
Zhong Y, Wu CF. 1991. Altered synaptic plasticity in Drosophila memory mutants with a defective cyclic AMP cascade. Science (New York, NY 251(4990):198-201.