Two Methods to Analyze LRRK2 Functions Under Lysosomal Stress: The Measurements of Cathepsin Release and Lysosomal Enlargement

Leucine-rich repeat kinase 2 (LRRK2) is a causative gene product of autosomal-dominant Parkinson's disease and has been shown to play a role in lysosomal regulation. We have previously shown that endogenous LRRK2 recruited its substrates Rab8a and Rab10 onto overloaded lysosomes depending on their phosphorylation, which functioned in the suppression of lysosomal enlargement as well as the promotion of the exocytic release of lysosomal cathepsins. In this chapter, we introduce two methods to analyze cellular functions of LRRK2 upon exposure to lysosomal overload stress in RAW264.7 cells.