Parkinson’s VPS35[D620N] retromer lysosomal dysfunction induces LRRK2 mediated lysosomal association of RILPL1 and TMEM55B

The D620N VPS35 mutation disrupts retrograde endosome to Golgi retromer Trafficking. Thus causes lysosome dysfunction, enhances LRRK2 kinase activity and leads to Parkinson’s disease. We employed a LysoTag immunoprecipitation approach to assess how this impacts lysosomes using quantitative proteomics. The VPS35[D620N] mutation alters the expression of over 350 lysosomal proteins, and induces recruitment of LRRK2 phosphorylated Rab proteins to the lysosome, as well as the phosphoRab effector protein RILPL1.