---
OA_place: publisher
OA_type: hybrid
PlanS_conform: '1'
_id: '20188'
abstract:
- lang: eng
  text: Collective cell migration is coordinated by the front-to-rear intercellular
    propagation of EGFR-Ras-ERK pathway activation. However, the molecular mechanisms
    integrating front-to-rear information into this intercellular signaling cascade,
    particularly the determinants of cellular front-side specification, remain elusive.
    We visualized the activity of EGFR, Ras, Rac1 and Rab5A (hereafter Rab5) by using
    FRET biosensors and chemogenetic tools. Whereas EGFR activation was uniformly
    observed within cells, Ras activation was biased to the front side within cells.
    The polarized Ras activation depended on Merlin and Rac1, which also showed front-biased
    activation. Furthermore, Rab5, a crucial regulator of cell migration, demonstrated
    similar front-biased activation and was found to function downstream of Ras while
    being necessary for Rac1 activation. Thus, the positive feedback loop consisting
    of Ras, Rab5 and Rac1 is activated primarily at the front of collectively migrating
    cells. These findings offer new spatio-temporal insight into processing front–rear
    information during collective cell migration.
acknowledgement: We are grateful to the members of the Matsuda Laboratory for their
  helpful input, to K. Hirano, T. Uesugi and K. Takakura, who provided technical assistance,
  and to the Medical Research Support Center of Kyoto University for DNA sequence
  analysis. This work was supported by the Kyoto University Live Imaging Center. Financial
  support was provided by Japan Society for the Promotion of Science (JSPS) KAKENHI
  grants (21H05226 to K.T., 19H00993 and 20H05898 to M.M.), a Japan Science and Technology
  Agency (JST) CREST grant (JPMJCR1654 to M.M.), and a JST Moonshot Research and Development
  Program grant (JPMJPS2022 to M.M.). Open Access funding provided by Tokushima University.
  Deposited in PMC for immediate release.
article_number: '263779'
article_processing_charge: Yes (via OA deal)
article_type: original
author:
- first_name: Yuya
  full_name: Jikko, Yuya
  last_name: Jikko
- first_name: Eriko
  full_name: Deguchi, Eriko
  last_name: Deguchi
- first_name: Kimiya
  full_name: Matsuda, Kimiya
  last_name: Matsuda
- first_name: Naoya
  full_name: Hino, Naoya
  id: 5299a9ce-7679-11eb-a7bc-d1e62b936307
  last_name: Hino
- first_name: Shinya
  full_name: Tsukiji, Shinya
  last_name: Tsukiji
- first_name: Michiyuki
  full_name: Matsuda, Michiyuki
  last_name: Matsuda
- first_name: Kenta
  full_name: Terai, Kenta
  last_name: Terai
citation:
  ama: Jikko Y, Deguchi E, Matsuda K, et al. Front-biased activation of the Ras-Rab5-Rac1
    loop coordinates collective cell migration. <i>Journal of Cell Science</i>. 2025;138(15).
    doi:<a href="https://doi.org/10.1242/jcs.263779">10.1242/jcs.263779</a>
  apa: Jikko, Y., Deguchi, E., Matsuda, K., Hino, N., Tsukiji, S., Matsuda, M., &#38;
    Terai, K. (2025). Front-biased activation of the Ras-Rab5-Rac1 loop coordinates
    collective cell migration. <i>Journal of Cell Science</i>. The Company of Biologists.
    <a href="https://doi.org/10.1242/jcs.263779">https://doi.org/10.1242/jcs.263779</a>
  chicago: Jikko, Yuya, Eriko Deguchi, Kimiya Matsuda, Naoya Hino, Shinya Tsukiji,
    Michiyuki Matsuda, and Kenta Terai. “Front-Biased Activation of the Ras-Rab5-Rac1
    Loop Coordinates Collective Cell Migration.” <i>Journal of Cell Science</i>. The
    Company of Biologists, 2025. <a href="https://doi.org/10.1242/jcs.263779">https://doi.org/10.1242/jcs.263779</a>.
  ieee: Y. Jikko <i>et al.</i>, “Front-biased activation of the Ras-Rab5-Rac1 loop
    coordinates collective cell migration,” <i>Journal of Cell Science</i>, vol. 138,
    no. 15. The Company of Biologists, 2025.
  ista: Jikko Y, Deguchi E, Matsuda K, Hino N, Tsukiji S, Matsuda M, Terai K. 2025.
    Front-biased activation of the Ras-Rab5-Rac1 loop coordinates collective cell
    migration. Journal of Cell Science. 138(15), 263779.
  mla: Jikko, Yuya, et al. “Front-Biased Activation of the Ras-Rab5-Rac1 Loop Coordinates
    Collective Cell Migration.” <i>Journal of Cell Science</i>, vol. 138, no. 15,
    263779, The Company of Biologists, 2025, doi:<a href="https://doi.org/10.1242/jcs.263779">10.1242/jcs.263779</a>.
  short: Y. Jikko, E. Deguchi, K. Matsuda, N. Hino, S. Tsukiji, M. Matsuda, K. Terai,
    Journal of Cell Science 138 (2025).
date_created: 2025-08-17T22:01:36Z
date_published: 2025-08-01T00:00:00Z
date_updated: 2025-11-27T14:12:24Z
day: '01'
ddc:
- '570'
department:
- _id: CaHe
doi: 10.1242/jcs.263779
external_id:
  isi:
  - '001567723900009'
  pmid:
  - '40667649'
file:
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  creator: dernst
  date_created: 2025-09-01T10:02:24Z
  date_updated: 2025-09-01T10:02:24Z
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file_date_updated: 2025-09-01T10:02:24Z
has_accepted_license: '1'
intvolume: '       138'
isi: 1
issue: '15'
language:
- iso: eng
license: https://creativecommons.org/licenses/by/4.0/
month: '08'
oa: 1
oa_version: Published Version
pmid: 1
publication: Journal of Cell Science
publication_identifier:
  eissn:
  - 1477-9137
  issn:
  - ' 0021-9533'
publication_status: published
publisher: The Company of Biologists
quality_controlled: '1'
scopus_import: '1'
status: public
title: Front-biased activation of the Ras-Rab5-Rac1 loop coordinates collective cell
  migration
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 138
year: '2025'
...