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.
LRRK2 controls synaptic vesicle storage and mobilization within the recycling pool / G. Piccoli, S.B. Condliffe, M. Bauer, F. Giesert, K. Boldt, S. De Astis, A. Meixner, H. Sarioglu, D.M. Vogt-Weisenhorn, W. Wurst, C.J. Gloeckner, M. Matteoli, C. Sala, M. Ueffing. - In: THE JOURNAL OF NEUROSCIENCE. - ISSN 0270-6474. - 31:6(2011 Feb), pp. 2225-2237.
LRRK2 controls synaptic vesicle storage and mobilization within the recycling pool
S. De Astis;M. Matteoli;
2011
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.File | Dimensione | Formato | |
---|---|---|---|
Piccoli et al..pdf
accesso aperto
Tipologia:
Pre-print (manoscritto inviato all'editore)
Dimensione
16.31 MB
Formato
Adobe PDF
|
16.31 MB | Adobe PDF | Visualizza/Apri |
2225.full.pdf
accesso aperto
Tipologia:
Publisher's version/PDF
Dimensione
2.65 MB
Formato
Adobe PDF
|
2.65 MB | Adobe PDF | Visualizza/Apri |
Pubblicazioni consigliate
I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.