LRRK2 controls synaptic vesicle storage and mobilization within the recycling pool

Giovanni Piccoli, Steven B. Condliffe, Matthias Bauer, Florian Giesert, Karsten Boldt, Silvia De Astis, Andrea Meixner, Hakan Sarioglu, Daniela M. Vogt-Weisenhorn, Wolfgang Wurst, Christian Johannes Gloeckner, Michela Matteoli, Carlo Sala, Marius Ueffing

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)2225-2237
Number of pages13
JournalJournal of Neuroscience
Volume31
Issue number6
DOIs
Publication statusPublished - Feb 9 2011

ASJC Scopus subject areas

  • Neuroscience(all)

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    Piccoli, G., Condliffe, S. B., Bauer, M., Giesert, F., Boldt, K., De Astis, S., Meixner, A., Sarioglu, H., Vogt-Weisenhorn, D. M., Wurst, W., Gloeckner, C. J., Matteoli, M., Sala, C., & Ueffing, M. (2011). LRRK2 controls synaptic vesicle storage and mobilization within the recycling pool. Journal of Neuroscience, 31(6), 2225-2237. https://doi.org/10.1523/JNEUROSCI.3730-10.2011