Exploring the Role of Rab12, the Enigmatic Player in Parkinson’s Disease, and its Regulation by the Newly Identified Crosstalk between LRRK2 and Protein Kinase Cb

Relying on our results that demonstrate a hitherto unknown crosstalk between LRRK2 and PKCb and distinguish the Rab12 complex with RILP, which comprises the non-phosphorylated form of Rab12, from its other complexes, we plan to focus in the present study on the following specific aims:

Ø Aim 1: Investigate the relationship between LRRK2 and PKCb. We aim to identify the specific PKCb isoform that acts in concert with LRRK2 and explore the underlying mechanism of their crosstalk.

Ø Aim 2: Identify the neuronal organelle(s), whose transport is controlled by the Rab12-RILP complex.

We hypothesize that the level of phosphorylated Rab12 dictates its distribution between its effectors, thereby influencing the transport of Rab12-regulated organelles.