Institute of Molecular and Cellular Biology & Department of Life Sciences

 

Dr. Oliver Wagner, Associate Professor

王歐力

副教授

My lab is interested in the regulation of organelle trafficking and molecular motors in the nervous system. We are using the model organism C. elegans with a fully sequenced genome.

In the image below, the nervous system of such a worm (1 mm in length) has been made visible by expressing a neuronal specific molecular motor (KIF1A/UNC-104). When zooming in, details of nerves and nerve bundles are evident including single cell bodies and long axonal extensions.

Time-lapse imaging reveals the bidirectional motility pattern of KIF1A/UNC-104. However, only little is known about the signals that trigger stops, starts and reversals of these molecular motors.

The nervous system of C. elegans is simple, yet, excellent for studying axonal transport due to the accessibility of very long axons (up to 500 microns) and the high homology of neuronal proteins compared to mammals.

Studying the regulation of motors becomes increasingly important as several motors are involved in various neurodegenerative diseases**:

Neurodegenerative disease

Involved molecular motors (and their adaptors)

• 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

• ALS (amyotrophic lateral sclerosis)
• Lissencephaly
• Lower motor neuron disease

Dynein (with adaptors dynactin and LIS1)

One of the basic questions regarding the regulation of molecular motors is how they recognize their cargo and how their motility is controlled.

Theories exist that molecular motors are activated by phosphorylation or, more interestingly, by binding to small regulatory proteins (adaptors). Recently, we have identified an (active zone) protein that facilitates anterograde movement when bound to UNC-104 (Wagner et al., PNAS, 2009).

One of our current projects focus on whether an additional linker would exist to connect the motor UNC-104 to a synaptic vesicle:

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

*The title image shows a worm double expressing a red fluorescent synaptic marker and green fluorescent molecular motors. The head of the worm faces to the left and the tail to the right. Head ganglia reveal strong colocalization between motor and cargo.

**Source: Hirokawa, N., et al., 2010. Molecular motors in neurons: transport mechanisms and roles in brain function, development, and disease. Neuron. 68, 610-38

 

Contact Information:

Oliver I. Wagner, PhD
Associate Professor
National Tsing Hua University
Institute of Molecular and Cellular Biology
Department of Life Science
101, Sec. 2, Kuang Fu Road
Hsinchu 30013
Taiwan (R. O. C.)
Tel: +886-3-574-2487
Fax: +886-3-571-5934
Email: owagner(at)life.nthu.edu.tw