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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 歐展言(Chan-Yen Ou) | |
| dc.contributor.author | Jhao-Ching Jhong | en |
| dc.contributor.author | 鍾昭慶 | zh_TW |
| dc.date.accessioned | 2021-06-17T02:44:28Z | - |
| dc.date.available | 2022-09-08 | |
| dc.date.copyright | 2017-09-08 | |
| dc.date.issued | 2017 | |
| dc.date.submitted | 2017-08-16 | |
| dc.identifier.citation | Ahmari, S.E., Buchanan, J., and Smith, S.J. (2000). Assembly of presynaptic active zones from cytoplasmic transport packets. Nat. Neurosci. 3, 445-451.
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/68963 | - |
| dc.description.abstract | 神經細胞向外伸長出樹突及軸突彼此連結。樹突負責接收來自突觸前神經的訊息，而軸突負責將訊息傳送給突觸後神經或肌肉。這兩種不同極性的功能需要不同的蛋白質及液胞(vesicle)來維持，而這些物質需要準確地分裝及運送。先前的研究發現少了CDK-5及PCT-1/CDK-16使得原本在軸突才需要的突觸小泡（synaptic vesicle）被錯誤地送到樹突。我們先前也發現當蛋白激酶A（PKA）過度活化時，也發生相同的現象。我的研究顯示蛋白激酶A與CDK-5及PCT-1/CDK-16作用在不同的訊息途徑中，並且過度活化蛋白激酶A不會影響樹突及軸突的型態及微管（mirotubule）的極性。即時影像分析（real-time imaging）的結果顯示蛋白激酶A活化了逆向運輸。
除了蛋白激酶A，鈣離子也調控了神經的運輸。我的研究顯示失去電位閘控型鈣離子通道不影響突觸小泡的極化運輸，但在缺少CYY-1、PCT-1及CDK-5的背景下，突觸小泡送到樹突的缺陷會變得更嚴重。失去神經傳遞也具有相同的現象。 這些結果顯示CDK及蛋白激酶A負責了細胞的極性運輸；而鈣離子負責維持突觸的正常功能。失去CDK及過度活化突觸小泡造成逆向運輸過度增強，而失去維持突觸正常功能的鈣離子流會讓失能的突觸小泡被過度增強的逆向運輸系統送去樹突。 | zh_TW |
| dc.description.abstract | In neuron, there are two polarized subcellular compartments, axons and dendrites. Dendrites receive signals from presynaptic neurons while axons release signals toward postsynaptic cells. In order to maintain the polarity and function of these subcellular compartments, proteins and vesicular cargos specific for axons or dendrites need to be precisely transported and targeted. In previous studies in C. elegans DA9 motor neuron, it was found that presynaptic components in axons mislocalize to dendrites in mutants of two cyclin dependent kinases pct-1/CDK-16 and cdk-5. In our previous study, a constitutively active mutant of G protein α-subunit gsa-1 enhanced cAMP-PKA signaling and resulted in similar mislocalizing phenotype. Here, I showed that GSA-1 acts independently with CDK-5 and CYY-1/PCT-1 without affecting neuronal morphology and microtubule polarity. In the dynamic imagine assay, I found that retrograde transport of synaptic vesicles in gsa-1 is stronger than wild type. The dynein heavy chain DHC-1 and its functional regulator NUD-2 are both required for gsa-1 mislocalizing phenotypes. These findings indicate that activation of cAMP-PKA signaling promotes retrograde movement of presynaptic components. Other than cAMP-PKA signaling, another secondary messenger Ca2+ was also reported to control synaptic function and morphology. I found that the depletion of an N and PQ-type Ca2+ channel (UNC-2) enhances the defect of pct-1, cyy-1 and cdk-5, and such enhancement seems to be the result of disrupting neuronal activity. Depleting neurotransmission in unc-18 mutants also strongly enhances the defect of pct-1. Together, these results suggest that secondary messengers are required to regulate polarized trafficking of synaptic vesicles, the disruption of secondary messenger signaling and neuronal activity will change the balance of polarized trafficking. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-17T02:44:28Z (GMT). No. of bitstreams: 1 ntu-106-R04442022-1.pdf: 5282056 bytes, checksum: 4999b4e8502ed497a5cd6bfd728fb212 (MD5) Previous issue date: 2017 | en |
| dc.description.tableofcontents | 論文審定書…………………………..…………………………………………………..i
中文摘要………………………………………………………………………………..ii ABSTRACT…………………………………………………………………………...iii TABLE OF CONTENTS……………………………………………………………....v I. NTRODUCTION…………………………………………………………………….1 1.1 Polarized trafficking in neuron………………………..……………………...1 1.2 Motor protein and intracellular transport……………………………………….2 1.3 Axonal transport and neuronal disorders……………………………………..4 1.4 The role of secondary messengers in neurons……………………………..4 II. MATERIALS AND METHODS……………………………………………………8 2.1 Strains and Genetics…………………………………………………………....8 2.2 Cloning and Constructs…………………………………………………………9 2.3 Combination of different genotypes…………………………………………..10 2.4 Worm lysis for genomic DNA...............................................................................11 2.5 Quantification…………………………………………………………………11 2.6 Dynamic imaging………………………………………………………………13 III. RESULTS…………………………………………………………………………14 3.1 Constitutively active PKA pathway disrupt synaptic vesicle localization………..14 3.2 GSA-1 functions in the independent pathway with PCT-1 and CDK-5………. ..16 3.3 GSA-1 do not change the morphology and axon-dendrite polarity in DA9…….17 3.4 GSA-1 promotes retrograde transport of SVs, requiring dynein components DHC-1 and NUD-2………………………………………………………………18 3.5 Calcium signaling component UNC-2 strongly enhance synaptic vesicle localization defect of pct-1, cyy-1 and cdk-5…………………………………19 3.6 The structure and localization defects of VGCC in active zone did not result in the enhancement of unc-2gk366…………………………………………………….20 3.7 The SV trafficking defect in pct-1; unc-2gk366 seemed to be the result of losing neuronal activity………………………………………………………………..22 3.8 Calmoduin dependent kinase suppress synaptic vesicle localization defect of cyy-1 and disrupted synapse morphology in axon of DA9 ………………….23 IV. DISCUSSION…………………………………………………………………….24 4.1 Downstream regulators of PKA signaling and CDK signaling…………………..25 4.2 The roles of Calcium signaling at presynaptic regions…………………………..25 4.3 CaMK regulates polarized postsynaptic cargo trafficking……………………….28 V. FIGURES……………………………………………………………………….....30 Figure 1. Activation the components of Gαs signaling pathway disrupted synaptic vesicle localization ………………….…………………...........32 Figure 2.GSA-1acted independently with cyy-1, pct-1 and cdk-5 signaling ………..34 Figure 3. gsa-1ce94 did not change the morphology and axon-dendrite polarity of DA9…………………………………………………………………..……36 Figure 4. GSA-1 promotes retrograde transport of SVP…………………………….39 Figure 5. unc-2gk366 strongly enhanced SV localization defect of pct-1, cyy-1, and cdk-5………………………………………………………………………42 Figure 6. The structure and localization defects of UNC-2 in active zone did not result in the enhancement of SV trafficking defect in pct-1;unc-2gk366………….45 Figure 7. unc-2gk366 enhancement seems to be the result of disrupting neurotransmission…………………………………………………………..47 Figure 8. unc-43e408 suppresses synaptic vesicle localization defect of cyy-1……….50 Figure 9. unc-43e408 disrupted synapse formation and localization of cyy-1………..52 VI. REFERENCE…………………………………………………………………....53 VII. APPENDIX……………………………………………………………………....70 7.1 Primers for genotyping and sequencing……………………………….......70 7.2 Constructs and transgenic worms………………………………………………..74 7.3 Plasmid sequences and cDNAs………………………………………………….78 | |
| dc.language.iso | en | |
| dc.subject | 突觸小泡定位 | zh_TW |
| dc.subject | UNC-18 | zh_TW |
| dc.subject | UNC-2 | zh_TW |
| dc.subject | CDK-5 | zh_TW |
| dc.subject | PCT-1 | zh_TW |
| dc.subject | 鈣離子訊息途徑 | zh_TW |
| dc.subject | cAMP-PKA 訊息途徑 | zh_TW |
| dc.subject | Gαs signaling | en |
| dc.subject | UNC-2 | en |
| dc.subject | CDK-5 | en |
| dc.subject | PCT-1 | en |
| dc.subject | calcium signaling | en |
| dc.subject | synaptic vesicle localization | en |
| dc.subject | UNC-18 | en |
| dc.subject | cAMP-PKA signaling | en |
| dc.title | 次級傳訊分子與蛋白激酶如何調控神經細胞內的極性化運輸 | zh_TW |
| dc.title | The study of how secondary messengers and protein kinases regulate neuronal polarized trafficking | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 105-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 蔡欣祐,黃憲松 | |
| dc.subject.keyword | 突觸小泡定位,cAMP-PKA 訊息途徑,鈣離子訊息途徑,PCT-1,CDK-5,UNC-2,UNC-18, | zh_TW |
| dc.subject.keyword | synaptic vesicle localization,Gαs signaling,cAMP-PKA signaling,PCT-1,CDK-5,UNC-2,calcium signaling,UNC-18, | en |
| dc.relation.page | 90 | |
| dc.identifier.doi | 10.6342/NTU201703484 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2017-08-16 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 生物化學暨分子生物學研究所 | zh_TW |
| 顯示於系所單位： | 生物化學暨分子生物學科研究所 | |
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