regulation of molecular motors and axonal transport in the...

Regulation of molecular motors and axonal transport in the nervous system of C. elegans

線蟲神經系統的分子運動與軸突運輸之調控機轉Lab’s Profile_______________________________________________________________________________:

Dr. Oliver I. Wagner王歐力博士Associate Professor, 副教授Institute of Molecular and Cellular Biology,

Department of Life Science, 生科系分生所National Tsing Hua University,國立清華大學Hsinchu, Taiwan.台灣新竹Life Science Building I, 5th Floor, Room No.: 507.

生科一館五樓507室http://life.nthu.edu.tw/~laboiw/

Members:Post-Doctoral Graduate博士後:1. 吳恭和Doctoral Students博士生:1. 陳志瑋2. Muniesh M. Shanmugam

3. Prerana Bhan

Master Students碩士生:1. Victor Daniel Lee Aplicano

2. 王鼎

Under-Graduate Students

學士班:1. 謝佳穎2. 徐千惠3. 李惠珉4. 張孟群5. 黃斯柔6. 謝予涵

Our Research_______________________________________________________________________________:

Why use C. elegans? C. elegans as a good model organism:

為什麼選擇「線蟲」作為模式生物？UNC-104 motor protein regulation and Tug-of-War:

UNC-104 運動蛋白的與調控機轉與「拔河之戰」：

Mitochondrial transport regulation in neurons:

粒線體在神經細胞的運輸機轉：

Ciliogenesis and Intra-Flagellar transport regulation:

「纖毛生成」與「內鞭毛運輸」的調控機轉：

• C. elegans has a very short life span, so several

generations can be analyzed.

• 線蟲有較短的生命週期，故利於作為模式生物來分析多代變異。

• Transparent body has an advantage of in vivo

monitoring of fluorescence tagged proteins.

• 透明的身體利於「活體觀察」用螢光標記之特定蛋白。

• C. elegans’ genome has been sequenced completely.

• 線蟲的基因體序列已被完全解構。• Several genetic-based studies are possible.

• 有多種以遺傳操作為基礎之研究工具可用。• C. elegans is very cost effective to maintain in any

laboratory.

• 線蟲模式系統的費用相對便宜以利多重研究。

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Neurodegenerative Disease Involved Molecular Motors

• Alzheimer’s disease, Huntington’s disease, Spastic paraplegia. Kinesin-1 (with adaptors APP and Huntingtin)

• Charcot-Marie-Tooth disease, Multiple sclerosis, Senile dementia. Kinesin-3

• Amyotrophic lateral sclerosis, Lissencephaly, Lower motor neuron

disease

Dynein (with adaptor dynactin and LIS1)Figure legend: A) C. elegans worms in Nematode Growth Medium, B) Short life cycle of C.

elegans & C) Transparent C. elegans expressing proteins tagged with GFP and mRFP.

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Figure legend: A) Kymograph of

UNC-104 molecular motor in C.

elegans axon, B) Shows differential

UNC-104 clustering between Wild-

type and mutant & C) Pictorial

representation of different theories

of cellular transport & Table: Shows

the involvement of molecular

motors in neurodegenerative

diseases.

Publications:• Chia, P. H., M. R. Patel, O. I. Wagner, D. R. Klopfenstein and K. Shen. 2013. Intramolecular regulation of presynaptic scaffold protein SYD-2/liprin-a.Mol. Cell Neurosci. 56:76-84.

• Tien, N.-W., G.-H. Wu, C.-C. Hsu, C.-Y. Chang and O. I. Wagner*. 2011. Tau/PTL-1 associates with kinesin-3 KIF1A/UNC-104 and affects the motor’s motility characteristics inC. elegans neurons. Neurobiol.Dis. 43:495-506.

• Hsu, C.-C., J. D. Moncaleano and O. I. Wagner*. 2011. Sub-cellular distribution of UNC-104(KIF1A) upon binding to adaptors as UNC-16(JIP3), DNC-1(DCTN1/Glued) and SYD-2(liprin-a) in C. elegans neurons. Neuroscience176:39-52.

• Wagner, O. I.*, A. Esposito, B. Köhler, C.-W. Chen, C.-P. Shen, G.-H. Wu, S. Mandalapu, D. Wenzel, F. S. Wouters and D. R. Klopfenstein*. 2009. Synaptic scaffolding protein SYD-2 clusters and activates kinesin-3 UNC-104 in C. elegans. Proc. Natl. Acad.

Sci. U S A 106:19605-19610. * Corresponding author.

Funding:• MOST 104-2321-B-007-008- (1/4) (PI) 台灣線蟲核心實驗室：整合、保存、與推廣線蟲生物資源與專業研究技術 (Integration, conservation, and distribution of C. elegans bio-resource and research know-how via the CECF Taiwan) 2015/01/01-

2015/12/31NTD 4,500,000 (to 3 PIs).

• MOST 103-2311-B-007 -004 -MY3 (PI) 藉由秀麗隱桿線蟲的神經系統來探討分子馬達對於囊泡運輸調控之協調性與拔河性機轉 (Understanding vesicle trafficking powered by coordinated activity and tug-of-war of molecular motors in neurons of C. elegansanimals) 2014/08/01-2017/07/31 NTD 5,850,000

• NSC 103-2321-B-007-007- (PI) 灣線蟲核心設施：轉型並因應快速成長的線蟲科學研究社群 (A C. elegans core facility to support the vast growing worm community in Taiwan) 2014/01/01-2014/12/31 NTD 1,447,800 to OIW (total NTD 3,800,000 to 3 PIs)

• NSC 102-2311-B-007-006- (PI) 線蟲感覺神經細胞內調控鞭毛內運輸及軸突運輸之分子機制 (Molecular mechanisms governing intraflagellar and axonal transport in C. elegans sensory neurons): 2013/08/01-2014/07/31 NTD 1,150,000• NSC 102-2321-B-002-071- (Co-PI) 邁向台灣線蟲核心設施之永續發展 (Toward the sustainable development of Taiwan C. elegans core facility): 2013/01/01-2013/12/31 NTD 980,000 to OIW (total NTD 2,854,500 to 3 PIs)• NSC 101-2311-B-007-002- (PI) 神經細胞內調控分子馬達與粒線體運輸的分子機制 (Molecular mechanisms underlying the regulation of kinesins and mitochondria transport in neurons): 2012/08/01-2013/07/31 NTD 1,150,000• NSC 101-2321-B-002-043- (Co-PI) 整合核心設施支援並提昇台灣線蟲研究 (An integrated core facility to foster and serve the Taiwan C. elegans community):2012/01/01-2012/12/31 NTD 840,000 to OIW (total NTD 3,000,000 to 3 PIs)

粒線體在神經細胞的運輸機轉： 「纖毛生成」與「內鞭毛運輸」的調控機轉：

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Figure legend: A) Pictorial representation of mitochondria linked with molecular motors (kinesin and

dynein) with adaptor proteins upon microtubule tracks, B) Kymograph of mitochondrial movement

(arrows) in neurons of C. elegans & C) C. elegans head sensory neuron showing mitochondria that express

GFP.

Figure legend: A) Pictorial representation of structure of cilia and Intra-flagellar transport of cargo inside the cilia, B) Shows localization of OSM-

3::GFP in cilia of sensory neurons of C. elegans in Wild type worm & C &D) abnormal clustering of OSM-3::GFP in mutant alleles at cilia. Dashed

lines represent the separation of distal and middle segment of cilia.