帳號:guest(3.231.3.140)          離開系統
字體大小: 字級放大   字級縮小   預設字形  

詳目顯示

以作者查詢圖書館館藏以作者查詢臺灣博碩士論文系統以作者查詢全國書目
作者(中文):吳恭和
作者(外文):Wu, Gong Her
論文名稱(中文):在線蟲神經系統中探討 LIN-2, SYD-2 及 MAP1-A 對於 Kinesin-3 UNC-104 移動機制之調節
論文名稱(外文):Mechanistic insights on the effects of LIN-2, SYD-2 and MAP1-A on kinesin-3 UNC-104 motility in the nervous system of C. elegans
指導教授(中文):王歐力
指導教授(外文):Oliver Wagner
口試委員(中文):汪宏達
焦傳金
黃兆祺
莊碧簪
學位類別:博士
校院名稱:國立清華大學
系所名稱:分子與細胞生物研究所
學號:9580820
出版年(民國):104
畢業學年度:103
語文別:中文英文
論文頁數:80
中文關鍵詞:UNC-104SYD-2LIN-2MAP-1Akinesin
外文關鍵詞:UNC-104SYD-2LIN-2MAP-1Akinesin
相關次數:
  • 推薦推薦:0
  • 點閱點閱:69
  • 評分評分:*****
  • 下載下載:8
  • 收藏收藏:0
線蟲之UNC-104屬於kinesin-3 蛋白家族,是哺乳類KIF1A的同源基因。 UNC-104 主要功能為參與神經系統中快速軸突突觸囊泡之運輸,並且對於神經細胞的生存與可塑性扮演相當重要的角色。目前,文獻中關於UNC-104活性之調控機制細節並不詳盡,因此我專注於研究UNC-104的活化以及不同蛋白質對於UNC-104功能的影響。我在本論文中指出LIN-2 (CASK) 及SYD-2 (liprin-α) 與UNC-104作用時,這兩個蛋白與UNC-104的結合位置是相互重疊的。在本論文中,我藉由酵母菌雙雜合實驗(Yeast two-hybrid)及免疫沉澱分析(co-immunoprecipitation assays)歸納出UNC-104/LIN-2, SYD-2/LIN-2 及 MAP-1A/LIN-2蛋白之間相互作用時彼此的結合區域。我更進一步利用雙分子螢光互補分析BiFC (bimolecular fluorescence complementation)研究上述蛋白質在線蟲中的結合作用以及結合後的蛋白質複合物在生物體中的位置。線蟲中UNC-104移動速度分析實驗指出在lin-2 的突變株中,UNC-104及其貨物(cargo)的標定蛋白SNB-1傳送速度會明顯的減慢,而此現象無法藉由SYD-2蛋白 大量表現彌補。 另外在lin-2 knock out /syd-2 knock down 的雙突變株中,UNC-104減慢的現象並未因此加劇。這些實驗結果顯示,LIN-2 與SYD-2 是作用在相同UNC-104調節路徑上,且LIN-2與SYD-2 需要同時存在才得以正確調控UNC-104之功能。另外,本論文中也提及MAP-1A (microtubule-associate protein 1A) 也同樣由與LIN-2 的結合作用影響UNC-104 與微管(microtubule)的接觸並進一步影響UNC-104的移動速度。因此,我歸納出LIN-2為調控UNC-104蛋白之運輸功能的樞紐。
ABSTRACT
UNC-104 (KIF1A) is a neuron-specific kinesin-3 which mainly involved in synaptic vesicles rapid axonal transport. While the function of this motor is of critical importance for neuronal viability and plasticity, little is known about how the motor is regulated. In this thesis, I identified a LIN-2 (CASK) binding site on UNC-104 which overlaps with that of SYD-2 (liprin-α) binding domain. Yeast two-hybrid (Y2H) and co-immunoprecipitation (co-IP) assays reveal specific interaction domains between UNC-104/LIN-2, SYD-2/LIN-2 and MAP-1A(microtubule-associate protein 1A)/LIN-2. These in vitro interactions were further confirmed by using in vivo BiFC (bimolecular fluorescence complementation) assay in living C. elegans. UNC-104 motility, as well as transportation rate of UNC-104 specific cargo, SNB-1 cargo, is significantly diminished in LIN-2 knockout (KO) worms, and this effect cannot be compensated by overexpressing UNC-104’s activator protein SYD-2. Moreover, the diminishing effect on UNC-104 motility can’t be further enhanced in LIN-2 KO/SYD-2 KD worm. These data reveal that LIN-2 and SYD-2 both act in the same UNC-104 regulation pathway and both LIN-2 and SYD-2 are essential for orchestration on activating UNC-104. Lastly, MAP-1A mediated UNC-104 transport characteristics depending on LIN-2, suggesting that LIN-2 plays a central role in regulating kinesin-3 UNC-104.
Table of Contents

ACKNOWLEDGEMENTS III
摘 要 IV
ABSTRACT V
TABLE OF CONTENTS VI
LIST OF FIGURES IX
LIST OF TABLES XI
1. INTRODUCTION 1
1-1 KINESIN-3 MOTOR KIF1A/UNC-104 2
1-2 ACTIVE ZONE PROTEIN SYD-2 4
1-3 CALCIUM/CALMODULIN-DEPENDENT SERINE PROTEIN KINASE (CASK)/LIN-2 5
1-4 MICROTUBULE-ASSOCIATED PROTEINS (MAPS)-MEDIATED REGULATION OF MOTOR PROTEINS 6
1-5 SPECIFIC AIMS 7
2. MATERIALS AND METHODS 8
2-1 C. ELEGANS STRAINS AND PLASMIDS 8
2-2 RNA INTERFERENCE 10
2-3 RNA ISOLATION 10
2-4 CDNA SYNTHESIS 11
2-5 REAL-TIME POLYMERASE CHAIN REACTION (PCR) 12
2-6 YEAST TWO-HYBRID ASSAY 12
2-7 PROTEIN EXTRACTION 13
2-8 CO-IMMUNOPRECIPITATION (CO-IP) ASSAYS 14
2-9 IMMUNOHISTOCHEMISTRY 15
2-10 MOTOR MOTILITY ANALYSIS 16
2-11 PRIMARY NEURON CULTURE 17
3. RESULTS 18
3-1 CHARACTERIZATION AND EXPRESSION STUDY OF C. ELEGANS LIN-2 18
3-2 FUNCTIONAL INTERACTIONS BETWEEN LIN-2 AND UNC-104 19
3-3 LIN-2 AFFECTS SIZE AND DISTRIBUTION OF AXONAL UNC-104 EN PASSANT CLUSTER 21
3-4 DIFFERENTIAL EFFECTS OF LIN-2 KO ON UNC-104 MOTILITY 22
3-5 LIN-2 MUTATIONS CAUSE SYNAPTIC VESICLE RETENTION IN THE SOMA OF NEURONS 24
3-6 INTERACTIONS BETWEEN LIN-2 AND SYD-2 25
3-7 LIN-2 AND SYD-2 ACT IN THE SAME PATHWAY WITH LIN-2 BEING THE MAJOR EFFECTOR OF UNC-104 26
3-8 THE PRESENCE OF MAP-1A IS ESSENTIAL FOR LIN-2’S MOTOR ACTIVATING EFFECT 27
4. DISCUSSION 29
4-1 MECHANISMS OF MOTOR PROTEIN REGULATION 29
4-2 INTERACTION SCHEME OF THE LIN-2/SYD-2/UNC-104/MAP-1A COMPLEX 30
4-3 ANTAGONISTIC EFFECTS OF LIN-2 AND SYD-2 ON THE REGULATION OF UNC-104 MOTOR CLUSTERING 32
4-4 LIN-2 AND SYD-2 ACT IN A COMPLEX TO FACILITATE UNC-104 POSSESSIVITY 33
4-5 THE EFFECT OF MAP-1A ON LIN-2’S MOTOR REGULATING FUNCTION 35
5. BIBLIOGRAPHY 37
6. FIGURES 44
7. TABLES 77
8. VITAE 80

. Baas, P.W., et al., Polarity orientation of microtubules in hippocampal neurons: uniformity in the axon and nonuniformity in the dendrite. Proc Natl Acad Sci U S A, 1988. 85(21): p. 8335-9.
2. Millecamps, S. and J.P. Julien, Axonal transport deficits and neurodegenerative diseases. Nat Rev Neurosci, 2013. 14(3): p. 161-76.
3. Barlan, K., M.J. Rossow, and V.I. Gelfand, The journey of the organelle: teamwork and regulation in intracellular transport. Curr Opin Cell Biol, 2013. 25(4): p. 483-8.
4. Salehi, A., J.D. Delcroix, and W.C. Mobley, Traffic at the intersection of neurotrophic factor signaling and neurodegeneration. Trends Neurosci, 2003. 26(2): p. 73-80.
5. Chevalier-Larsen, E. and E.L. Holzbaur, Axonal transport and neurodegenerative disease. Biochim Biophys Acta, 2006. 1762(11-12): p. 1094-108.
6. Goldstein, L.S., Axonal transport and neurodegenerative disease: can we see the elephant? Prog Neurobiol, 2012. 99(3): p. 186-90.
7. Charrin, B.C., F. Saudou, and S. Humbert, Axonal transport failure in neurodegenerative disorders: the case of Huntington's disease. Pathol Biol (Paris), 2005. 53(4): p. 189-92.
8. Goldstein, L.S., Kinesin molecular motors: transport pathways, receptors, and human disease. Proc Natl Acad Sci U S A, 2001. 98(13): p. 6999-7003.
9. Mandelkow, E. and E.M. Mandelkow, Kinesin motors and disease. Trends Cell Biol, 2002. 12(12): p. 585-91.
10. Hirokawa, N., S. Niwa, and Y. Tanaka, Molecular motors in neurons: transport mechanisms and roles in brain function, development, and disease. Neuron, 2010. 68(4): p. 610-38.
11. Maeder, C.I., et al., In vivo neuron-wide analysis of synaptic vesicle precursor trafficking. Traffic, 2013.
12. Yonekawa, Y., et al., Defect in synaptic vesicle precursor transport and neuronal cell death in KIF1A motor protein-deficient mice. J Cell Biol, 1998. 141(2): p. 431-41.
13. Klebe, S., et al., KIF1A missense mutations in SPG30, an autosomal recessive spastic paraplegia: distinct phenotypes according to the nature of the mutations. Eur J Hum Genet, 2012. 20(6): p. 645-9.
14. Riviere, J.B., et al., KIF1A, an axonal transporter of synaptic vesicles, is mutated in hereditary sensory and autonomic neuropathy type 2. Am J Hum Genet, 2011. 89(2): p. 219-30.
15. Hamdan, F.F., et al., Excess of de novo deleterious mutations in genes associated with glutamatergic systems in nonsyndromic intellectual disability. Am J Hum Genet, 2011. 88(3): p. 306-16.
16. Hall, D.H. and E.M. Hedgecock, Kinesin-related gene unc-104 is required for axonal transport of synaptic vesicles in C. elegans. Cell, 1991. 65(5): p. 837-47.
17. Kern, J.V., et al., The kinesin-3, unc-104 regulates dendrite morphogenesis and synaptic development in Drosophila. Genetics, 2013. 195(1): p. 59-72.
18. Rashid, D.J., et al., Monomeric and dimeric states exhibited by the kinesin-related motor protein KIF1A. J Pept Res, 2005. 65(6): p. 538-49.
19. Huo, L., et al., The CC1-FHA tandem as a central hub for controlling the dimerization and activation of kinesin-3 KIF1A. Structure, 2012. 20(9): p. 1550-61.
20. Hammond, J.W., et al., Mammalian Kinesin-3 motors are dimeric in vivo and move by processive motility upon release of autoinhibition. PLoS Biol, 2009. 7(3): p. e72.
21. Klopfenstein, D.R., et al., Role of phosphatidylinositol(4,5)bisphosphate organization in membrane transport by the Unc104 kinesin motor. Cell, 2002. 109(3): p. 347-58.
22. Goodwin, P.R. and P. Juo, The scaffolding protein SYD-2/Liprin-alpha regulates the mobility and polarized distribution of dense-core vesicles in C. elegans motor neurons. PLoS One, 2013. 8(1): p. e54763.
23. Zhen, M. and Y. Jin, The liprin protein SYD-2 regulates the differentiation of presynaptic termini in C. elegans. Nature, 1999. 401(6751): p. 371-5.
24. Chia, P.H., et al., Intramolecular regulation of presynaptic scaffold protein SYD-2/liprin-alpha. Mol Cell Neurosci, 2013. 56: p. 76-84.
25. Shin, H., et al., Association of the kinesin motor KIF1A with the multimodular protein liprin-alpha. J Biol Chem, 2003. 278(13): p. 11393-401.
26. Spangler, S.A., et al., Liprin-alpha2 promotes the presynaptic recruitment and turnover of RIM1/CASK to facilitate synaptic transmission. J Cell Biol, 2013. 201(6): p. 915-28.
27. Hsu, C.C., J.D. Moncaleano, and O.I. Wagner, Sub-cellular distribution of UNC-104(KIF1A) upon binding to adaptors as UNC-16(JIP3), DNC-1(DCTN1/Glued) and SYD-2(Liprin-alpha) in C. elegans neurons. Neuroscience, 2011. 176: p. 39-52.
28. Wagner, O.I., et al., Synaptic scaffolding protein SYD-2 clusters and activates kinesin-3 UNC-104 in C. elegans. Proc Natl Acad Sci U S A, 2009. 106(46): p. 19605-10.
29. Dai, Y., et al., SYD-2 Liprin-alpha organizes presynaptic active zone formation through ELKS. Nat Neurosci, 2006. 9(12): p. 1479-87.
30. Ko, J., et al., Interaction between liprin-alpha and GIT1 is required for AMPA receptor targeting. J Neurosci, 2003. 23(5): p. 1667-77.
31. Olsen, O., et al., Neurotransmitter release regulated by a MALS-liprin-alpha presynaptic complex. J Cell Biol, 2005. 170(7): p. 1127-34.
32. Zheng, C.Y., et al., MAGUKs, synaptic development, and synaptic plasticity. Neuroscientist, 2011. 17(5): p. 493-512.
33. Maximov, A., T.C. Sudhof, and I. Bezprozvanny, Association of neuronal calcium channels with modular adaptor proteins. J Biol Chem, 1999. 274(35): p. 24453-6.
34. Setou, M., et al., Kinesin superfamily motor protein KIF17 and mLin-10 in NMDA receptor-containing vesicle transport. Science, 2000. 288(5472): p. 1796-802.
35. Tabuchi, K., et al., CASK participates in alternative tripartite complexes in which Mint 1 competes for binding with caskin 1, a novel CASK-binding protein. J Neurosci, 2002. 22(11): p. 4264-73.
36. Hsueh, Y.P., The role of the MAGUK protein CASK in neural development and synaptic function. Curr Med Chem, 2006. 13(16): p. 1915-27.
37. Borg, J.P., et al., Identification of an evolutionarily conserved heterotrimeric protein complex involved in protein targeting. J Biol Chem, 1998. 273(48): p. 31633-6.
38. Butz, S., M. Okamoto, and T.C. Sudhof, A tripartite protein complex with the potential to couple synaptic vesicle exocytosis to cell adhesion in brain. Cell, 1998. 94(6): p. 773-82.
39. Olsen, O., et al., Synaptic transmission regulated by a presynaptic MALS/Liprin-alpha protein complex. Curr Opin Cell Biol, 2006. 18(2): p. 223-7.
40. Asaba, N., et al., Direct interaction with a kinesin-related motor mediates transport of mammalian discs large tumor suppressor homologue in epithelial cells. J Biol Chem, 2003. 278(10): p. 8395-400.
41. Schnapp, B.J., Trafficking of signaling modules by kinesin motors. J Cell Sci, 2003. 116(Pt 11): p. 2125-35.
42. Amos, L.A. and D. Schlieper, Microtubules and maps. Adv Protein Chem, 2005. 71: p. 257-98.
43. Kosik, K.S. and L. McConlogue, Microtubule-associated protein function: lessons from expression in Spodoptera frugiperda cells. Cell Motil Cytoskeleton, 1994. 28(3): p. 195-8.
44. Baas, P.W., et al., Tau confers drug stability but not cold stability to microtubules in living cells. J Cell Sci, 1994. 107 ( Pt 1): p. 135-43.
45. Brandt, R. and G. Lee, Functional organization of microtubule-associated protein tau. Identification of regions which affect microtubule growth, nucleation, and bundle formation in vitro. J Biol Chem, 1993. 268(5): p. 3414-9.
46. Tien, N.W., et al., Tau/PTL-1 associates with kinesin-3 KIF1A/UNC-104 and affects the motor's motility characteristics in C. elegans neurons. Neurobiol Dis, 2011. 43(2): p. 495-506.
47. Barlan, K., W. Lu, and V.I. Gelfand, The microtubule-binding protein ensconsin is an essential cofactor of kinesin-1. Curr Biol, 2013. 23(4): p. 317-22.
48. Mandelkow, E.M., et al., MARK/PAR1 kinase is a regulator of microtubule-dependent transport in axons. J Cell Biol, 2004. 167(1): p. 99-110.
49. Seitz, A., et al., Single-molecule investigation of the interference between kinesin, tau and MAP2c. EMBO J, 2002. 21(18): p. 4896-905.
50. Vershinin, M., et al., Multiple-motor based transport and its regulation by Tau. Proc Natl Acad Sci U S A, 2007. 104(1): p. 87-92.
51. Halpain, S. and L. Dehmelt, The MAP1 family of microtubule-associated proteins. Genome Biol, 2006. 7(6): p. 224.
52. Reese, M.L., et al., The guanylate kinase domain of the MAGUK PSD-95 binds dynamically to a conserved motif in MAP1a. Nat Struct Mol Biol, 2007. 14(2): p. 155-63.
53. Brenner, S., The genetics of Caenorhabditis elegans. Genetics, 1974. 77(1): p. 71-94.
54. Hoskins, R., et al., The C. elegans vulval induction gene lin-2 encodes a member of the MAGUK family of cell junction proteins. Development, 1996. 122(1): p. 97-111.
55. Timmons, L. and A. Fire, Specific interference by ingested dsRNA. Nature, 1998. 395(6705): p. 854.
56. Hoogewijs, D., et al., Selection and validation of a set of reliable reference genes for quantitative sod gene expression analysis in C. elegans. BMC Mol Biol, 2008. 9: p. 9.
57. Ward, S., et al., Genomic organization of major sperm protein genes and pseudogenes in the nematode Caenorhabditis elegans. J Mol Biol, 1988. 199(1): p. 1-13.
58. Schneider, C.A., W.S. Rasband, and K.W. Eliceiri, NIH Image to ImageJ: 25 years of image analysis. Nat Methods, 2012. 9(7): p. 671-5.
59. Duerr, J.S., Immunohistochemistry. WormBook, 2006: p. 1-61.
60. Kumar, J., et al., The Caenorhabditis elegans Kinesin-3 motor UNC-104/KIF1A is degraded upon loss of specific binding to cargo. PLoS Genet, 2010. 6(11): p. e1001200.
61. Christensen, M., et al., A primary culture system for functional analysis of C. elegans neurons and muscle cells. Neuron, 2002. 33(4): p. 503-14.
62. Strange, K., M. Christensen, and R. Morrison, Primary culture of Caenorhabditis elegans developing embryo cells for electrophysiological, cell biological and molecular studies. Nat Protoc, 2007. 2(4): p. 1003-12.
63. Xia, X., DAMBE5: a comprehensive software package for data analysis in molecular biology and evolution. Mol Biol Evol, 2013. 30(7): p. 1720-8.
64. McGee, A.W., et al., Structure of the SH3-guanylate kinase module from PSD-95 suggests a mechanism for regulated assembly of MAGUK scaffolding proteins. Mol Cell, 2001. 8(6): p. 1291-301.
65. Shin, H., et al., An intramolecular interaction between Src homology 3 domain and guanylate kinase-like domain required for channel clustering by postsynaptic density-95/SAP90. J Neurosci, 2000. 20(10): p. 3580-7.
66. Wu, H., et al., Intramolecular interactions regulate SAP97 binding to GKAP. EMBO J, 2000. 19(21): p. 5740-51.
67. Qian, Y. and K.E. Prehoda, Interdomain interactions in the tumor suppressor discs large regulate binding to the synaptic protein GukHolder. J Biol Chem, 2006. 281(47): p. 35757-63.
68. Hu, C.D. and T.K. Kerppola, Simultaneous visualization of multiple protein interactions in living cells using multicolor fluorescence complementation analysis. Nat Biotechnol, 2003. 21(5): p. 539-45.
69. Kerppola, T.K., Design and implementation of bimolecular fluorescence complementation (BiFC) assays for the visualization of protein interactions in living cells. Nat Protoc, 2006. 1(3): p. 1278-86.
70. Zheng, Q., et al., The Vesicle Protein SAM-4 Regulates the Processivity of Synaptic Vesicle Transport. PLoS Genet, 2014. 10(10): p. e1004644.
71. Perlson, E., et al., Retrograde axonal transport: pathways to cell death? Trends Neurosci, 2010. 33(7): p. 335-44.
72. Franker, M.A. and C.C. Hoogenraad, Microtubule-based transport - basic mechanisms, traffic rules and role in neurological pathogenesis. J Cell Sci, 2013. 126(Pt 11): p. 2319-29.
73. Akhmanova, A. and J.A. Hammer, 3rd, Linking molecular motors to membrane cargo. Curr Opin Cell Biol, 2010. 22(4): p. 479-87.
74. Maeder, C.I., K. Shen, and C.C. Hoogenraad, Axon and dendritic trafficking. Curr Opin Neurobiol, 2014. 27C: p. 165-170.
75. Tomishige, M., D.R. Klopfenstein, and R.D. Vale, Conversion of Unc104/KIF1A kinesin into a processive motor after dimerization. Science, 2002. 297(5590): p. 2263-7.
76. Doerks, T., et al., L27, a novel heterodimerization domain in receptor targeting proteins Lin-2 and Lin-7. Trends Biochem Sci, 2000. 25(7): p. 317-8.
77. Wei, Z., et al., Liprin-mediated large signaling complex organization revealed by the liprin-alpha/CASK and liprin-alpha/liprin-beta complex structures. Mol Cell, 2011. 43(4): p. 586-98.
78. Zurner, M. and S. Schoch, The mouse and human Liprin-alpha family of scaffolding proteins: genomic organization, expression profiling and regulation by alternative splicing. Genomics, 2009. 93(3): p. 243-53.
79. Taru, H. and Y. Jin, The Liprin homology domain is essential for the homomeric interaction of SYD-2/Liprin-alpha protein in presynaptic assembly. J Neurosci, 2011. 31(45): p. 16261-8.
80. Nix, S.L., et al., hCASK and hDlg associate in epithelia, and their src homology 3 and guanylate kinase domains participate in both intramolecular and intermolecular interactions. J Biol Chem, 2000. 275(52): p. 41192-200.
81. Wu, Y.E., et al., The balance between capture and dissociation of presynaptic proteins controls the spatial distribution of synapses. Neuron, 2013. 78(6): p. 994-1011.
82. Soppina, V., et al., Dimerization of mammalian kinesin-3 motors results in superprocessive motion. Proc Natl Acad Sci U S A, 2014. 111(15): p. 5562-7.
83. Harterink, M. and C.C. Hoogenraad, Slide to the left and slide to the right: motor coordination in neurons. Dev Cell, 2013. 26(4): p. 326-8.
84. Wyszynski, M., et al., Interaction between GRIP and liprin-alpha/SYD2 is required for AMPA receptor targeting. Neuron, 2002. 34(1): p. 39-52.
85. Liu, J.S., et al., Molecular basis for specific regulation of neuronal kinesin-3 motors by doublecortin family proteins. Mol Cell, 2012. 47(5): p. 707-21.
86. Seog, D.H., Glutamate receptor-interacting protein 1 protein binds to the microtubule-associated protein. Biosci Biotechnol Biochem, 2004. 68(8): p. 1808-10.
87. Jimenez-Mateos, E.M., et al., Binding of microtubule-associated protein 1B to LIS1 affects the interaction between dynein and LIS1. Biochem J, 2005. 389(Pt 2): p. 333-41.
88. Huang, J., et al., Lis1 acts as a "clutch" between the ATPase and microtubule-binding domains of the dynein motor. Cell, 2012. 150(5): p. 975-86.
 
 
 
 
第一頁 上一頁 下一頁 最後一頁 top

相關論文

1. 透過細胞骨架與突觸前驅因子調節軸突的快速運輸
2. Visualization of Direct Protein Interactions in the Nervous System of C. elegans Using the BiFC Assay
3. Visualization of interactions between molecular motors and their adaptors in the nervous system of C. elegans using the BiFC assay
4. Protein with Tau-Like Repeats (PTL-1) Is a Cargo for KIF1A/UNC-104 and Regulates Its Transport Characteristics
5. 研究SNB-1和RAB-3在線蟲神經系統中的軸突運輸
6. 在線蟲神經系統中LIN-2與UNC-104的交互作用及其活化UNC-104運動能力的分子機制
7. Dynein和dynactin在突觸囊泡運輸以及在KIF1A/UNC-104的聚集與運輸中所扮演的角色
8. 研究中間絲蛋白IFB-1在線蟲amphid神經中對粒線體運輸之影響
9. 探討磷酸激酶及磷酸酶影響線蟲神經纖毛生成及纖毛內運輸機制的可能性
10. 探討秀麗隱桿線蟲在dynein和dynactin變異下軸突中UNC-104的聚集與運輸
11. 研究激酶GCK-2及PKG-1對線蟲神經纖毛生成及鞭毛內運輸機制之影響調控
12. Identification of an intermediate filament TAG-63 affecting fast axonal transport in Caenorhabditis elegans
13. 線蟲中肌凝蛋白-V同源蛋白HUM-2之特性
14. 第一章: 線蟲三聯複合體RAB-3-UNC-10-SYD-2之活性區調控驅動蛋白-3 UNC-104的作用角色 第二章: PKG-1與GCK-2 能調節線蟲感覺神經之纖毛長度與鞭毛內運輸 第三章: 線蟲中似神經絲蛋白TAG-63能促進神經軸突傳遞機制
15. 探討線蟲神經突觸缺失如何改變微管轉譯後修飾與軸突運輸
 
* *