Editing of Kinesin Heavy Chain to Elucidate its roles in Neurodegenerative Diseases
Physical and Biological Sciences
Molecular, Cell and Developmental Biology
Neurons are highly specialized and complicated cells. Neurons are composed of a cell body with dendrites that receive signals and a long axon that sends signals. Cellular metabolites, such as mRNAs and proteins, must be transported down the axon of neurons since the majority of them are synthesized solely in the cell body. Axonal transport is carried out by motor proteins, such as dynein and kinesin, that walk along microtubules carrying cargo from the cell body. Motor neuron degenerative diseases have been linked to disruptions in axonal transport from defective motor proteins. To study both the basic mechanism of axonal transport and related neurodegenerative diseases we used gene editing tools to change parts of the kinesin heavy chain (Khc) protein that are involved in kinesin regulation and that are known to cause Hereditary Spastic Paraplegia (HSP) in humans. I have already been successful in creating two different mutations in the Drosophila kinesin gene involved in kinesin autoregulation. These mutant flies have been tested and were shown to have a disruption in axonal transport. With the completion of ongoing experiments, these mutations will allow for a more in depth understanding of kinesin autoregulation. Investigating the basic functions of kinesin will aid in the development of therapeutic strategies for motor neuron degenerative diseases.
