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The function of Golgi apparatus in LRRK2-associated Parkinson’s disease

Parkinson’s disease (PD) is a chronic neurodegenerative disease associated with the intracellular organelles. Leucine-rich repeat kinase 2 (LRRK2) is a large multi-structural domain protein, and mutation in LRRK2 is associated with PD. LRRK2 regulates intracellular vesicle transport and function of...

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Autores principales: Wei, Yonghang, Awan, Maher un Nisa, Bai, Liping, Bai, Jie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9989030/
https://www.ncbi.nlm.nih.gov/pubmed/36896008
http://dx.doi.org/10.3389/fnmol.2023.1097633
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author Wei, Yonghang
Awan, Maher un Nisa
Bai, Liping
Bai, Jie
author_facet Wei, Yonghang
Awan, Maher un Nisa
Bai, Liping
Bai, Jie
author_sort Wei, Yonghang
collection PubMed
description Parkinson’s disease (PD) is a chronic neurodegenerative disease associated with the intracellular organelles. Leucine-rich repeat kinase 2 (LRRK2) is a large multi-structural domain protein, and mutation in LRRK2 is associated with PD. LRRK2 regulates intracellular vesicle transport and function of organelles, including Golgi and lysosome. LRRK2 phosphorylates a group of Rab GTPases, including Rab29, Rab8, and Rab10. Rab29 acts in a common pathway with LRRK2. Rab29 has been shown to recruit LRRK2 to the Golgi complex (GC) to stimulate LRRK2 activity and alter the Golgi apparatus (GA). Interaction between LRRK2 and Vacuolar protein sorting protein 52 (VPS52), a subunit of the Golgi-associated retrograde protein (GARP) complex, mediates the function of intracellular soma trans-Golgi network (TGN) transport. VPS52 also interacts with Rab29. Knockdown of VPS52 leads to the loss of LRRK2/Rab29 transported to the TGN. Rab29, LRRK2, and VPS52 work together to regulate functions of the GA, which is associated with PD. We highlight recent advances in the roles of LRRK2, Rabs, VPS52, and other molecules, such as Cyclin-dependent kinase 5 (CDK5) and protein kinase C (PKC) in the GA, and discuss their possible association with the pathological mechanisms of PD.
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spelling pubmed-99890302023-03-08 The function of Golgi apparatus in LRRK2-associated Parkinson’s disease Wei, Yonghang Awan, Maher un Nisa Bai, Liping Bai, Jie Front Mol Neurosci Neuroscience Parkinson’s disease (PD) is a chronic neurodegenerative disease associated with the intracellular organelles. Leucine-rich repeat kinase 2 (LRRK2) is a large multi-structural domain protein, and mutation in LRRK2 is associated with PD. LRRK2 regulates intracellular vesicle transport and function of organelles, including Golgi and lysosome. LRRK2 phosphorylates a group of Rab GTPases, including Rab29, Rab8, and Rab10. Rab29 acts in a common pathway with LRRK2. Rab29 has been shown to recruit LRRK2 to the Golgi complex (GC) to stimulate LRRK2 activity and alter the Golgi apparatus (GA). Interaction between LRRK2 and Vacuolar protein sorting protein 52 (VPS52), a subunit of the Golgi-associated retrograde protein (GARP) complex, mediates the function of intracellular soma trans-Golgi network (TGN) transport. VPS52 also interacts with Rab29. Knockdown of VPS52 leads to the loss of LRRK2/Rab29 transported to the TGN. Rab29, LRRK2, and VPS52 work together to regulate functions of the GA, which is associated with PD. We highlight recent advances in the roles of LRRK2, Rabs, VPS52, and other molecules, such as Cyclin-dependent kinase 5 (CDK5) and protein kinase C (PKC) in the GA, and discuss their possible association with the pathological mechanisms of PD. Frontiers Media S.A. 2023-02-21 /pmc/articles/PMC9989030/ /pubmed/36896008 http://dx.doi.org/10.3389/fnmol.2023.1097633 Text en Copyright © 2023 Wei, Awan, Bai and Bai. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neuroscience
Wei, Yonghang
Awan, Maher un Nisa
Bai, Liping
Bai, Jie
The function of Golgi apparatus in LRRK2-associated Parkinson’s disease
title The function of Golgi apparatus in LRRK2-associated Parkinson’s disease
title_full The function of Golgi apparatus in LRRK2-associated Parkinson’s disease
title_fullStr The function of Golgi apparatus in LRRK2-associated Parkinson’s disease
title_full_unstemmed The function of Golgi apparatus in LRRK2-associated Parkinson’s disease
title_short The function of Golgi apparatus in LRRK2-associated Parkinson’s disease
title_sort function of golgi apparatus in lrrk2-associated parkinson’s disease
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9989030/
https://www.ncbi.nlm.nih.gov/pubmed/36896008
http://dx.doi.org/10.3389/fnmol.2023.1097633
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