Role of LRRK2 in the regulation of dopamine receptor trafficking

Mauro Rassu, Maria Grazia Del Giudice, Simona Sanna, Jean Marc Taymans, Michele Morari, Alberto Brugnoli, Martina Frassineti, Alessandra Masala, Sonia Esposito, Manuela Galioto, Cristiana Valle, Maria Teresa Carri, Alice Biosa, Elisa Greggio, Claudia Crosio, Ciro Iaccarino

Research output: Contribution to journalArticle

16 Citations (Scopus)

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.

Original languageEnglish
Article numbere0179082
JournalPLoS One
Volume12
Issue number6
DOIs
Publication statusPublished - Jun 1 2017

Fingerprint

Dopamine Receptors
Parkinson Disease
Parkinson disease
Dopamine D1 Receptors
Physiology
Dopamine D2 Receptors
physiology
Golgi Apparatus
Signal transduction
mutants
receptors
Disease Progression
Signal Transduction
Cell membranes
Golgi apparatus
Cell Membrane
Pharmacology
cell membranes
signal transduction
Brain

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Rassu, M., Del Giudice, M. G., Sanna, S., Taymans, J. M., Morari, M., Brugnoli, A., ... Iaccarino, C. (2017). Role of LRRK2 in the regulation of dopamine receptor trafficking. PLoS One, 12(6), [e0179082]. https://doi.org/10.1371/journal.pone.0179082

Role of LRRK2 in the regulation of dopamine receptor trafficking. / Rassu, Mauro; Del Giudice, Maria Grazia; Sanna, Simona; Taymans, Jean Marc; Morari, Michele; Brugnoli, Alberto; Frassineti, Martina; Masala, Alessandra; Esposito, Sonia; Galioto, Manuela; Valle, Cristiana; Carri, Maria Teresa; Biosa, Alice; Greggio, Elisa; Crosio, Claudia; Iaccarino, Ciro.

In: PLoS One, Vol. 12, No. 6, e0179082, 01.06.2017.

Research output: Contribution to journalArticle

Rassu, M, Del Giudice, MG, Sanna, S, Taymans, JM, Morari, M, Brugnoli, A, Frassineti, M, Masala, A, Esposito, S, Galioto, M, Valle, C, Carri, MT, Biosa, A, Greggio, E, Crosio, C & Iaccarino, C 2017, 'Role of LRRK2 in the regulation of dopamine receptor trafficking', PLoS One, vol. 12, no. 6, e0179082. https://doi.org/10.1371/journal.pone.0179082
Rassu M, Del Giudice MG, Sanna S, Taymans JM, Morari M, Brugnoli A et al. Role of LRRK2 in the regulation of dopamine receptor trafficking. PLoS One. 2017 Jun 1;12(6). e0179082. https://doi.org/10.1371/journal.pone.0179082
Rassu, Mauro ; Del Giudice, Maria Grazia ; Sanna, Simona ; Taymans, Jean Marc ; Morari, Michele ; Brugnoli, Alberto ; Frassineti, Martina ; Masala, Alessandra ; Esposito, Sonia ; Galioto, Manuela ; Valle, Cristiana ; Carri, Maria Teresa ; Biosa, Alice ; Greggio, Elisa ; Crosio, Claudia ; Iaccarino, Ciro. / Role of LRRK2 in the regulation of dopamine receptor trafficking. In: PLoS One. 2017 ; Vol. 12, No. 6.
@article{2f969f7087e943389d30fae2d52f95b6,
title = "Role of LRRK2 in the regulation of dopamine receptor trafficking",
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.",
author = "Mauro Rassu and {Del Giudice}, {Maria Grazia} and Simona Sanna and Taymans, {Jean Marc} and Michele Morari and Alberto Brugnoli and Martina Frassineti and Alessandra Masala and Sonia Esposito and Manuela Galioto and Cristiana Valle and Carri, {Maria Teresa} and Alice Biosa and Elisa Greggio and Claudia Crosio and Ciro Iaccarino",
year = "2017",
month = "6",
day = "1",
doi = "10.1371/journal.pone.0179082",
language = "English",
volume = "12",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "6",

}

TY - JOUR

T1 - Role of LRRK2 in the regulation of dopamine receptor trafficking

AU - Rassu, Mauro

AU - Del Giudice, Maria Grazia

AU - Sanna, Simona

AU - Taymans, Jean Marc

AU - Morari, Michele

AU - Brugnoli, Alberto

AU - Frassineti, Martina

AU - Masala, Alessandra

AU - Esposito, Sonia

AU - Galioto, Manuela

AU - Valle, Cristiana

AU - Carri, Maria Teresa

AU - Biosa, Alice

AU - Greggio, Elisa

AU - Crosio, Claudia

AU - Iaccarino, Ciro

PY - 2017/6/1

Y1 - 2017/6/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85020462209&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85020462209&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0179082

DO - 10.1371/journal.pone.0179082

M3 - Article

C2 - 28582422

AN - SCOPUS:85020462209

VL - 12

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 6

M1 - e0179082

ER -