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Role of LRRK2 in the regulation of dopamine receptor trafficking

Rassu, Mauro and Del Giudice, Maria Grazia and Sanna, Simona and Taymans, Jean-Marc and Morari, Michele and Brugnoli, Alberto and Frassineti, Martina and Masala, Alessandra and Esposito, Sonia and Galioto, Manuela and Valle, Cristiana and Carri, Maria Teresa and Biosa, Alice and Greggio, Elisa and Crosio, Claudia and Iaccarino, Ciro (2017) Role of LRRK2 in the regulation of dopamine receptor trafficking. PLoS One, Vol. 12 (6), e0179082. ISSN 1932-6203. Article.

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DOI: 10.1371/journal.pone.0179082

Abstract

Mutations in LRRK2 play a critical role in both familial and sporadic Parkinson’s disease (PD). Up to date, the role of LRRK2 in PD onset and progression remains largely unknown. However, experimental evidence highlights a critical role of LRRK2 in the control of vesicle trafficking that in turn may regulate different aspects of neuronal physiology. We have analyzed the role of LRRK2 in regulating dopamine receptor D1 (DRD1) and D2 (DRD2) trafficking. DRD1 and DRD2 are the most abundant dopamine receptors in the brain. They differ in structural, pharmacological and biochemical properties, as well as in localization and internalization mechanisms. Our results indicate that disease-associated mutant G2019S LRRK2 impairs DRD1 internalization, leading to an alteration in signal transduction. Moreover, the mutant forms of LRRK2 affect receptor turnover by decreasing the rate of DRD2 trafficking from the Golgi complex to the cell membrane. Collectively, our findings are consistent with the conclusion that LRRK2 influences the motility of neuronal vesicles and the neuronal receptor trafficking. These findings have important implications for the complex role that LRRK2 plays in neuronal physiology and the possible pathological mechanisms that may lead to neuronal death in PD.

Item Type:Article
ID Code:11797
Status:Published
Refereed:Yes
Uncontrolled Keywords:Dopamine, membrane trafficking, neurons, cell membranes, vesicles, membrane proteins, Parkinson disease, receptor physiology
Subjects:Area 05 - Scienze biologiche > BIO/11 Biologia molecolare
Divisions:001 Università di Sassari > 01-a Nuovi Dipartimenti dal 2012 > Scienze Biomediche
Publisher:Public Library of Science
ISSN:1932-6203
Copyright Holders:© 2017 Rassu et al.
Deposited On:25 Sep 2017 17:08

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