PT  - JOURNAL ARTICLE
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
TI  - LRRK2 Controls Synaptic Vesicle Storage and Mobilization within the Recycling Pool
AID  - 10.1523/JNEUROSCI.3730-10.2011
DP  - 2011 Feb 09
TA  - The Journal of Neuroscience
PG  - 2225--2237
VI  - 31
IP  - 6
4099  - http://www.jneurosci.org/content/31/6/2225.short
4100  - http://www.jneurosci.org/content/31/6/2225.full
SO  - J. Neurosci.2011 Feb 09; 31
AB  - 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.