Leucine-Rich Repeat Kinase 2 (Lrrk2)-Sensitive Na/K ATPase Activity in Dendritic Cells.

Leucine-rich repeat kinase 2 (Lrrk2) has been implicated in the pathophysiology of Parkinson's disease. Lrrk2 is expressed in diverse cells including neurons and dendritic cells (DCs). In DCs Lrrk2 was shown to up-regulate Na/Ca-exchanger activity. The elimination of Ca by Na/Ca -exchangers requires maintenance of the Na gradient by the Na/K -ATPase. The present study thus explored whether Lrrk2 impacts on Na/K -ATPase expression and function. To this end DCs were isolated from gene-targeted mice lacking Lrrk2 (Lrrk2) and their wild-type littermates (Lrrk2). Na/K -ATPase activity was estimated from K induced, ouabain sensitive, current determined by whole cell patch clamp. Na/K -ATPase α1 subunit transcript and protein levels were determined by RT-qPCR and flow cytometry. As a result, the K induced current was significantly smaller in Lrrk2 than in Lrrk2 DCs and was completely abolished by ouabain (100 μM) in both genotypes. The K induced, ouabain sensitive, current in Lrrk2 DCs was significantly blunted by Lrrk2 inhibitor GSK2578215A (1 μM, 24 hours). The Na/K -ATPase α1 subunit transcript and protein levels were significantly lower in Lrrk2 than in Lrrk2 DCs and significantly decreased by Lrrk2 inhibitor GSK2578215A (1 μM, 24 hours). In conclusion, Lrrk2 is a powerful regulator of Na/K -ATPase expression and activity in dendritic cells.