LRRK2 Affects Vesicle Trafficking, Neurotransmitter Extracellular Level and Membrane Receptor Localization
Copyright policy )LRRK2 Affects Vesicle Trafficking, Neurotransmitter Extracellular Level and Membrane Receptor Localization
The leucine-rich repeat kinase 2 (LRRK2) gene was found to play a role in the pathogenesis of both familial and sporadic Parkinson's disease (PD). LRRK2 encodes a large multi-domain protein that is expressed in different tissues. To date, the physiological and pathological functions of LRRK2 are not clearly defined. In this study we have explored the role of LRRK2 in controlling vesicle trafficking in different cellular or animal models and using various readouts. In neuronal cells, the presence of LRRK2(G2019S) pathological mutant determines increased extracellular dopamine levels either under basal conditions or upon nicotine stimulation. Moreover, mutant LRRK2 affects the levels of dopamine receptor D1 on the membrane surface in neuronal cells or animal models. Ultrastructural analysis of PC12-derived cells expressing mutant LRRK2(G2019S) shows an altered intracellular vesicle distribution. Taken together, our results point to the key role of LRRK2 to control vesicle trafficking in neuronal cells.
- National Research Council Italy
- Johns Hopkins University School of Medicine United States
- University of Sassari Italy
- National Research Council Sri Lanka
- University of Rome Tor Vergata Italy
Science, Dopamine, Mutation, Missense, Protein-Serine-Threonine Kinase, Protein Serine-Threonine Kinases, Leucine-Rich Repeat Serine-Threonine Protein Kinase-2, PC12 Cells, Mice, Dopamine D1, Receptors, Animals, Humans, Parkinson, Settore BIO/10 - BIOCHIMICA, Neurons, Animal, Receptors, Dopamine D1, Q, Animals; Humans; Disease Models, Animal; Mice; Protein-Serine-Threonine Kinases; Mutation, Missense; Rats; Dopamine; Receptors, Dopamine D1; Parkinson Disease; Neurons; Amino Acid Substitution; PC12 Cells; Protein Transport, R, LRRK2, Parkinson Disease, Neuron, dardarina, PC12 Cell, Rats, Disease Models, Animal, Protein Transport, Amino Acid Substitution, Disease Models, Mutation, Rat, Medicine, Missense, dopamine, Human, Research Article
Science, Dopamine, Mutation, Missense, Protein-Serine-Threonine Kinase, Protein Serine-Threonine Kinases, Leucine-Rich Repeat Serine-Threonine Protein Kinase-2, PC12 Cells, Mice, Dopamine D1, Receptors, Animals, Humans, Parkinson, Settore BIO/10 - BIOCHIMICA, Neurons, Animal, Receptors, Dopamine D1, Q, Animals; Humans; Disease Models, Animal; Mice; Protein-Serine-Threonine Kinases; Mutation, Missense; Rats; Dopamine; Receptors, Dopamine D1; Parkinson Disease; Neurons; Amino Acid Substitution; PC12 Cells; Protein Transport, R, LRRK2, Parkinson Disease, Neuron, dardarina, PC12 Cell, Rats, Disease Models, Animal, Protein Transport, Amino Acid Substitution, Disease Models, Mutation, Rat, Medicine, Missense, dopamine, Human, Research Article
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