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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...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
National Academy of Sciences
2023
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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. |
format | Online Article Text |
id | pubmed-10614619 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | National Academy of Sciences |
record_format | MEDLINE/PubMed |
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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