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Pathological Functions of LRRK2 in Parkinson’s Disease
Open AccessArticle

LRRK2 Modulates the Exocyst Complex Assembly by Interacting with Sec8

1
Department of Biomedical Sciences, University of Sassari, 07100 Sassari, Italy
2
Nurex Srl, 07100 Sassari, Italy
3
Department of Oncology, University of Turin, 10126 Turin, Italy
4
Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
5
Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
6
Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
7
Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
8
Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
*
Author to whom correspondence should be addressed.
Present Address of Yulan Xiong: Department of Neuroscience, University of Connecticut School of Medicine, Farmington, CT 06030, USA.
Academic Editors: Michele Morari and Paolo Calabresi
Cells 2021, 10(2), 203; https://doi.org/10.3390/cells10020203
Received: 28 October 2020 / Revised: 12 January 2021 / Accepted: 18 January 2021 / Published: 20 January 2021
(This article belongs to the Special Issue LRRK2-Dependent Neurodegeneration in Parkinson’s Disease)
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, likely by Rab phosphorylation, that in turn may regulate different aspects of neuronal physiology. Here we show that LRRK2 interacts with Sec8, one of eight subunits of the exocyst complex. The exocyst complex is an evolutionarily conserved multisubunit protein complex mainly involved in tethering secretory vesicles to the plasma membrane and implicated in the regulation of multiple biological processes modulated by vesicle trafficking. Interestingly, Rabs and exocyst complex belong to the same protein network. Our experimental evidence indicates that LRRK2 kinase activity or the presence of the LRRK2 kinase domain regulate the assembly of exocyst subunits and that the over-expression of Sec8 significantly rescues the LRRK2 G2019S mutant pathological effect. Our findings strongly suggest an interesting molecular mechanism by which LRRK2 could modulate vesicle trafficking and may have important implications to decode the complex role that LRRK2 plays in neuronal physiology. View Full-Text
Keywords: LRRK2; Sec8; exocyst complex; Parkinson’s disease LRRK2; Sec8; exocyst complex; Parkinson’s disease
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MDPI and ACS Style

Fais, M.; Sanna, G.; Galioto, M.; Nguyen, T.T.D.; Trần, M.U.T.; Sini, P.; Carta, F.; Turrini, F.; Xiong, Y.; Dawson, T.M.; Dawson, V.L.; Crosio, C.; Iaccarino, C. LRRK2 Modulates the Exocyst Complex Assembly by Interacting with Sec8. Cells 2021, 10, 203. https://doi.org/10.3390/cells10020203

AMA Style

Fais M, Sanna G, Galioto M, Nguyen TTD, Trần MUT, Sini P, Carta F, Turrini F, Xiong Y, Dawson TM, Dawson VL, Crosio C, Iaccarino C. LRRK2 Modulates the Exocyst Complex Assembly by Interacting with Sec8. Cells. 2021; 10(2):203. https://doi.org/10.3390/cells10020203

Chicago/Turabian Style

Fais, Milena; Sanna, Giovanna; Galioto, Manuela; Nguyen, Thi T.D.; Trần, Mai U.T.; Sini, Paola; Carta, Franco; Turrini, Franco; Xiong, Yulan; Dawson, Ted M.; Dawson, Valina L.; Crosio, Claudia; Iaccarino, Ciro. 2021. "LRRK2 Modulates the Exocyst Complex Assembly by Interacting with Sec8" Cells 10, no. 2: 203. https://doi.org/10.3390/cells10020203

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