TY - JOUR T1 - LRRK2 Controls Synaptic Vesicle Storage and Mobilization within the Recycling Pool JF - The Journal of Neuroscience JO - J. Neurosci. SP - 2225 LP - 2237 DO - 10.1523/JNEUROSCI.3730-10.2011 VL - 31 IS - 6 AU - Giovanni Piccoli AU - Steven B. Condliffe AU - Matthias Bauer AU - Florian Giesert AU - Karsten Boldt AU - Silvia De Astis AU - Andrea Meixner AU - Hakan Sarioglu AU - Daniela M. Vogt-Weisenhorn AU - Wolfgang Wurst AU - Christian Johannes Gloeckner AU - Michela Matteoli AU - Carlo Sala AU - Marius Ueffing Y1 - 2011/02/09 UR - http://www.jneurosci.org/content/31/6/2225.abstract N2 - Mutations in leucine-rich repeat kinase 2 (LRRK2) are the single most common cause of inherited Parkinson's disease. Little is known about its involvement in the pathogenesis of Parkinson's disease mainly because of the lack of knowledge about the physiological role of LRRK2. To determine the function of LRRK2, we studied the impact of short hairpin RNA-mediated silencing of LRRK2 expression in cortical neurons. Paired recording indicated that LRRK2 silencing affects evoked postsynaptic currents. Furthermore, LRRK2 silencing induces at the presynaptic site a redistribution of vesicles within the bouton, altered recycling dynamics, and increased vesicle kinetics. Accordingly, LRRK2 protein is present in the synaptosomal compartment of cortical neurons in which it interacts with several proteins involved in vesicular recycling. Our results suggest that LRRK2 modulates synaptic vesicle trafficking and distribution in neurons and in consequence participates in regulating the dynamics between vesicle pools inside the presynaptic bouton. ER -