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Membrane remodeling properties of the Parkinson’s disease protein LRRK2

Mutations in Leucine-rich repeat kinase 2 (LRRK2) are responsible for late-onset autosomal dominant Parkinson’s disease. LRRK2 has been implicated in a wide range of physiological processes including membrane repair in the endolysosomal system. Here, using cell-free systems, we report that purified...

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Autores principales: Wang, Xinbo, Espadas, Javier, Wu, Yumei, Cai, Shujun, Ge, Jinghua, Shao, Lin, Roux, Aurélien, De Camilli, Pietro
Formato: Online Artículo Texto
Lenguaje:English
Publicado: National Academy of Sciences 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10614619/
https://www.ncbi.nlm.nih.gov/pubmed/37844218
http://dx.doi.org/10.1073/pnas.2309698120
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author Wang, Xinbo
Espadas, Javier
Wu, Yumei
Cai, Shujun
Ge, Jinghua
Shao, Lin
Roux, Aurélien
De Camilli, Pietro
author_facet Wang, Xinbo
Espadas, Javier
Wu, Yumei
Cai, Shujun
Ge, Jinghua
Shao, Lin
Roux, Aurélien
De Camilli, Pietro
author_sort Wang, Xinbo
collection PubMed
description Mutations in Leucine-rich repeat kinase 2 (LRRK2) are responsible for late-onset autosomal dominant Parkinson’s disease. LRRK2 has been implicated in a wide range of physiological processes including membrane repair in the endolysosomal system. Here, using cell-free systems, we report that purified LRRK2 directly binds acidic lipid bilayers with a preference for highly curved bilayers. While this binding is nucleotide independent, LRRK2 can also deform low-curvature liposomes into narrow tubules in a guanylnucleotide-dependent but Adenosine 5′-triphosphate-independent way. Moreover, assembly of LRRK2 into scaffolds at the surface of lipid tubules can constrict them. We suggest that an interplay between the membrane remodeling and signaling properties of LRRK2 may be key to its physiological function. LRRK2, via its kinase activity, may achieve its signaling role at sites where membrane remodeling occurs.
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spelling pubmed-106146192023-10-31 Membrane remodeling properties of the Parkinson’s disease protein LRRK2 Wang, Xinbo Espadas, Javier Wu, Yumei Cai, Shujun Ge, Jinghua Shao, Lin Roux, Aurélien De Camilli, Pietro Proc Natl Acad Sci U S A Biological Sciences Mutations in Leucine-rich repeat kinase 2 (LRRK2) are responsible for late-onset autosomal dominant Parkinson’s disease. LRRK2 has been implicated in a wide range of physiological processes including membrane repair in the endolysosomal system. Here, using cell-free systems, we report that purified LRRK2 directly binds acidic lipid bilayers with a preference for highly curved bilayers. While this binding is nucleotide independent, LRRK2 can also deform low-curvature liposomes into narrow tubules in a guanylnucleotide-dependent but Adenosine 5′-triphosphate-independent way. Moreover, assembly of LRRK2 into scaffolds at the surface of lipid tubules can constrict them. We suggest that an interplay between the membrane remodeling and signaling properties of LRRK2 may be key to its physiological function. LRRK2, via its kinase activity, may achieve its signaling role at sites where membrane remodeling occurs. National Academy of Sciences 2023-10-16 2023-10-24 /pmc/articles/PMC10614619/ /pubmed/37844218 http://dx.doi.org/10.1073/pnas.2309698120 Text en Copyright © 2023 the Author(s). Published by PNAS. https://creativecommons.org/licenses/by/4.0/This open access article is distributed under Creative Commons Attribution License 4.0 (CC BY) (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Biological Sciences
Wang, Xinbo
Espadas, Javier
Wu, Yumei
Cai, Shujun
Ge, Jinghua
Shao, Lin
Roux, Aurélien
De Camilli, Pietro
Membrane remodeling properties of the Parkinson’s disease protein LRRK2
title Membrane remodeling properties of the Parkinson’s disease protein LRRK2
title_full Membrane remodeling properties of the Parkinson’s disease protein LRRK2
title_fullStr Membrane remodeling properties of the Parkinson’s disease protein LRRK2
title_full_unstemmed Membrane remodeling properties of the Parkinson’s disease protein LRRK2
title_short Membrane remodeling properties of the Parkinson’s disease protein LRRK2
title_sort membrane remodeling properties of the parkinson’s disease protein lrrk2
topic Biological Sciences
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10614619/
https://www.ncbi.nlm.nih.gov/pubmed/37844218
http://dx.doi.org/10.1073/pnas.2309698120
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