ssbd-repos-000365

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Slow diffusion and signal amplification on membranes regulated by phospholipase D

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ssbd-repos-000365
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DOI

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Title
Slow diffusion and signal amplification on membranes regulated by phospholipase D
Description
Control of molecular diffusion is pivotal for highly fluidic membranes to serve as substrates for biochemical reactions and the self-assembly of molecular machinery driving membrane protrusions. Lateral diffusion in membranes depends on lipid composition, which is highly diverse and homeostatically controlled in living cells. Due to the complexity of the underlying processes, its impact on molecular diffusion remain largely unclear. In this study, we show that lipid diffusion in model membranes is markedly decreased in cytosolic extracts. The reduction in lipid diffusivity could be pharmacologically inhibited by targeting phospholipase D (PLD), and addition of PLD to membranes mimicked the reduction in diffusion. Phosphatidic acid, a direct product of PLD, diffused slowly in model membranes and reduced the diffusivity of surrounding lipids. Furthermore, we demonstrated that PLD specifically controls the lateral diffusion of a myristoylated protein in cells, possibly due to auxiliary electrostatic interactions between cationic residues located near the lipidated tail and anionic phospholipids. PLD controlled the size and lifetime of localized patches of phosphatidylinositol (3,4,5)-trisphosphates that specify regions of membrane protrusions. Overall, the results of this study suggest that PLD controls the lateral diffusion of certain membrane proteins, which play key roles in phosphoinositide signaling.
Submission date
2024-07-11
Release date
2026-05-13
Update date
-
License
CC BY-NC license
Funding information
This work was supported by grants from the Japan Science and Technology Agency (JST), CREST (JPMJCR1923, S. S.), FOREST (JPMJFR213Y, M. Y.), and the Japan Society for the Promotion of Science (JSPS) KAKENHI (JP22H01188, M. Y. and JP19H05801, S. S.).
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Papers
https://www.biorxiv.org/content/10.1101/2024.07.08.602473v1 , https://doi.org/10.1101/2024.07.08.602473
Honda, Gen, Tanaka, Chihuku, Sawai, Satoshi, Yanagisawa, Miho (2024/01/01), Slow diffusion and signal amplification on membranes regulated by phospholipase D, bioRxiv, 2024.07.08.602473
https://doi.org/10.1073/pnas.2608790123 PMID: 42127117
Gen Honda, Chihuku Tanaka, Hidenori Hashimura, Tomoko Adachi, Mina Fujishiro, Nao Shimada, Satoshi Sawai, Miho Yanagisawa (2026) Phospholipase D regulates on-membrane diffusivity of a myristoylated protein and defines the PIP3 patch territory., Proceedings of the National Academy of Sciences of the United States of America, Volume 123, Number 20, pp. e2608790123

Persons

Gen Honda
University of Tokyo
Contact

Ontology terms

Organism
Dictyostelium discoideum
Strain
AX2, AX4
Cell line
-
Molecular function
-
Biological process
-
Cellular component
-
Medical subject heading
-
Biological imaging method
confocal microscopy, FRAP

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