Investigating the Role of a Truncated LRRK2 Product in Parkinsons Disease
One million Americans suffer from Parkinson’s Disease (PD), a fatal neurodegenerative disorder characterized by neuronal death and motor symptoms such as bradykinesia and tremors. Unfortunately, there is no treatment that prevents, reverses or even delays PD. My research focuses on the protein called the Leucine Rich Repeat Kinase 2 (LRRK2), which is the most common site for mutations in PD. However, the mechanism by which LRRK2 causes PD is unknown. With the help of my lab at UCSF, I have uncovered that a sizable amount of intracellular LRRK2 is processed to a shorter ~160 kD version of LRRK2 missing its N-terminus. This exciting piece of LRRK2 biology has remained unknown because the protein is lowly expressed in most cells. This project will define the shortened sequence of LRRK2, determine how it is generated in the cell, and begin to test its cellular functions. Specifically, I will test the hypotheses that an unidentified protease cleaves LRRK2 and that these two products have different functions.
Message to Sponsor
- Major: Molecular Cell Biology
- Sponsor: Thye L&S
- Mentor: Jen-Chywan Wang