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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.

LRRK2 controls synaptic vesicle storage and mobilization within the recycling pool.

J. Neurosci. 31, 2225-2237 (2011)
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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.
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Publication type Article: Journal article
Document type Scientific Article
Keywords READILY RELEASABLE POOL; REPEAT KINASE 2; CLATHRIN-MEDIATED ENDOCYTOSIS; CULTURED HIPPOCAMPAL-NEURONS; SINGLE-PARTICLE TRACKING; PAIRED-PULSE DEPRESSION; MOTOR-NERVE TERMINALS; PARKINSONS-DISEASE; SHORT-TERM; NEUROTRANSMITTER RELEASE
Language english
Publication Year 2011
HGF-reported in Year 2011
ISSN (print) / ISBN 0270-6474
e-ISSN 1529-2401
Journal Journal of Neuroscience
Quellenangaben Volume: 31, Issue: 6, Pages: 2225-2237 Article Number: , Supplement: ,
Publisher Society for Neuroscience
Reviewing status Peer reviewed
Institute(s) CF Metabolomics & Proteomics (CF-MPC)
Institute of Developmental Genetics (IDG)
POF-Topic(s) 30203 - Molecular Targets and Therapies
30204 - Cell Programming and Repair
Research field(s) Enabling and Novel Technologies
Genetics and Epidemiology
PSP Element(s) G-505700-001
G-500500-001
G-500500-003
PubMed ID 21307259
DOI 10.1523/JNEUROSCI.3730-10.2011
Scopus ID 79951534656
Erfassungsdatum 2011-08-11
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