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Scientific article
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English

Membrane remodeling properties of the Parkinson’s disease protein LRRK2

Publication date2023-10-16
First online date2023-10-16
Abstract

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.

eng
Keywords
  • GTPase
  • LRRK2
  • Parkinson
  • Membrane curvature
  • Tubulation
Research group
Funding
  • Aligning Science Across Parkinson's - Impaired integration of organelle function in Parkinson’s disease [ASAP-000580]
  • NIDA NIH HHS - [P30 DA018343]
  • EMBO-Long Term Fellowship - [ALT 989-2022]
  • Parkinson's Foundation - [PF-RCE-1946]
  • European Research Council - [951324-R2-TENSION]
  • HHS | NIH | NIDA | National Drug Abuse Treatment Clinical Trials Network - [P30DA018343]
  • Swiss National Science Foundation - [189996]
  • Swiss National Fund for research - [CRSII5_189996 310030_200793]
Citation (ISO format)
WANG, Xinbo et al. Membrane remodeling properties of the Parkinson’s disease protein LRRK2. In: Proceedings of the National Academy of Sciences of the United States of America, 2023, vol. 120, n° 43, p. e2309698120. doi: 10.1073/pnas.2309698120
Main files (1)
Article (Published version)
Identifiers
ISSN of the journal0027-8424
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Technical informations

Creation11/06/2023 12:12:15 PM
First validation11/08/2023 12:39:44 PM
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