Excitable Ras dynamics-based screens reveal RasGEFX is required for macropinocytosis and random cell migration

Iwamoto, Koji; Matsuoka, Satomi; Ueda, Masahiro

Nature Communications, 2025, 16, 117

Number of Access:319（2025-07-18 14:22 Counts）

Identifier to cite or link to this item: https://hdl.handle.net/11094/100431

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Title
Excitable Ras dynamics-based screens reveal RasGEFX is required for macropinocytosis and random cell migration
Creator
CreatorName
Iwamoto, Koji
NRID
1000000569733 1000000569733
ORCID
0000-0002-4552-4460 0000-0002-4552-4460
researchmap permalink
read0212004 read0212004
Scopus Author ID
7202477132 7202477132
CreatorName
Matsuoka, Satomi
NRID
1000040444517 1000040444517
ORCID
0000-0002-9354-3404 0000-0002-9354-3404
researchmap permalink
MasahiroUeda2018-SBC MasahiroUeda2018-SBC
Scopus Author ID
35303650000 35303650000
CreatorName
Ueda, Masahiro
Description
Iwamoto K., Matsuoka S., Ueda M. Excitable Ras dynamics-based screens reveal RasGEFX is required for macropinocytosis and random cell migration. Nature Communications 16, 117 (2025); https://doi.org/10.1038/s41467-024-55389-2.
Abstract
Excitable systems of eukaryotic chemotaxis can generate asymmetric signals of Ras-GTP-enriched domains spontaneously to drive random cell migration without guidance cues. However, the molecules responsible for the spontaneous signal generation remain elusive. Here, we characterized RasGEFs encoded in Dictyostelium discoideum by live-cell imaging of the spatiotemporal dynamics of Ras-GTP and hierarchical clustering, finding that RasGEFX is primarily required for the spontaneous generation of Ras-GTP-enriched domains and is essential for random migration in combination with RasGEFB/M/U in starved cells, and they are dispensable for chemotaxis to chemoattractant cAMP. RasGEFX and RasGEFB that co-localize with Ras-GTP regulate the temporal periods and spatial sizes of the oscillatory Ras-GTP waves propagating along the membrane, respectively, and thus control the protrusions of motile cells differently, while RasGEFU and RasGEFM regulate adhesion and migration speed, respectively. Remarkably, RasGEFX is also important for Ras/PIP3-driven macropinocytosis in proliferating cells, but RasGEFB/M/U are not. These findings illustrate a specific and coordinated control of the cytoskeletal dynamics by multiple RasGEFs for spontaneous motility and macropinocytosis.
Publisher
Nature Research
Source Title
Nature Communications
Volume (Issue)
16
Page
117
Date of Issued
2025-01-02
Language
English
Handle URL
https://hdl.handle.net/11094/100431
eISSN
20411723
Relation.isIdenticalTo
DOI (Publisher Version)
https://doi.org/10.1038/s41467-024-55389-2
Access Rights
open access
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This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
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Category
学術雑誌論文 Journal Article