Leucine-rich repeat kinase 2-sensitive Na+/Ca2+ exchanger activity in dendritic cells

Gene variants of the leucine-rich repeat kinase 2 (LRRK2) are associated with susceptibility to Parkinson's disease (PD). Besides brain and periphery, LRRK2 is expressed in various immune cells including dendritic cells (DCs), antigen-presenting cells linking innate and adaptive immunity. However, the function of LRRK2 in the immune system is still incompletely understood. Here, Ca2+-signaling was analyzed in DCs isolated from gene-targeted mice lacking lrrk2 (Lrrk2−/−) and their wild-type littermates (Lrrk2+/+). According to Western blotting, Lrrk2 was expressed in Lrrk2+/+ DCs but not in Lrrk2−/−DCs. Cytosolic Ca2+ levels ([Ca2+]i) were determined utilizing Fura-2 fluorescence and whole cell currents to decipher electrogenic transport. The increase of [Ca2+]i following inhibition of sarcoendoplasmatic Ca2+-ATPase with thapsigargin (1 µM) in the absence of extracellular Ca2+ (Ca2+-release) and the increase of [Ca2+]i following subsequent readdition of extracellular Ca2+ (SOCE) were both significantly lar...