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 2+ -exchanger activity. The elimination of Ca 2+ by Na + /Ca 2+ -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.