LRRK2 Controls Synaptic Vesicle Storage and Mobilization within the Recycling Pool
Copyright policy )LRRK2 Controls Synaptic Vesicle Storage and Mobilization within the Recycling Pool
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.
- Protein Sciences United States
- Technical University of Munich Germany
- University of Milan Italy
- Helmholtz Zentrum München Germany
- University of Otago New Zealand
Patch-Clamp Techniques, Nerve Tissue Proteins, Leucine-Rich Repeat Serine-Threonine Protein Kinase-2, Potassium Chloride, Mice, 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, Microscopy, Electron, Transmission, Animals, Humans, Immunoprecipitation, N-Ethylmaleimide-Sensitive Proteins, Cells, Cultured, Cerebral Cortex, Neurons, Analysis of Variance, 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, Excitatory Postsynaptic Potentials, Gene Expression Regulation, Developmental, Embryo, Mammalian, Electric Stimulation, Mutation, Calcium
Patch-Clamp Techniques, Nerve Tissue Proteins, Leucine-Rich Repeat Serine-Threonine Protein Kinase-2, Potassium Chloride, Mice, 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, Microscopy, Electron, Transmission, Animals, Humans, Immunoprecipitation, N-Ethylmaleimide-Sensitive Proteins, Cells, Cultured, Cerebral Cortex, Neurons, Analysis of Variance, 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, Excitatory Postsynaptic Potentials, Gene Expression Regulation, Developmental, Embryo, Mammalian, Electric Stimulation, Mutation, Calcium
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