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Peer-reviewedCC BY-NC-ND 4.0Journal of Cell Biology

Spatial inhibition of RhoA by RhoGAP15B promotes protrusive activity during collective migration

Abstract

The Rho family GTPases RhoA, Rac1, and Cdc42 are well-established regulators of collective migration by driving the formation of cellular protrusions and by regulating actomyosin contraction and adhesion. However, how their activation and inhibition are spatially and temporally coordinated remains unclear. Using GFP knock-in lines, we systematically characterized the localization patterns of all Drosophila RhoGEFs (activators) and RhoGAPs (inhibitors) in border cells, an in vivo model of collective migration. We have further combined RNAi screening with GFP-based validation of depletion efficiency to assess the functional significance of those RhoGEFs/GAPs expressed in border cells. This identified RhoGAP15B as a localized inhibitor of RhoA activity at the border cell cortex. RhoGAP15B regulates cluster morphology and is enriched at the leading cell front, where it restrains actomyosin contractility to promote protrusive behavior. Our findings reveal RhoGAP15B as a key spatial RhoA regulator and highlight that patterned RhoGAP and RhoGEF activities are essential for coordinating cortical contraction and protrusion dynamics during collective migration.

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BibTeX
@article{yang2026spatial,
  title = {{Spatial inhibition of RhoA by RhoGAP15B promotes protrusive activity during collective migration}},
  author = {Vítor Yang and Cristian Marchant and Bing Liu and Mariana Osswald and Jesus Lopez-Gay and Yohanns Bellaïche and Xiaobo Wang and Eurico Morais-De-Sá},
  journal = {Journal of Cell Biology},
  year = {2026},
  month = jun,
  doi = {10.1083/jcb.202511004},
  url = {https://hal.science/hal-05767951v1},
  note = {CC BY-NC-ND 4.0},
}
RIS
TY  - JOUR
TI  - Spatial inhibition of RhoA by RhoGAP15B promotes protrusive activity during collective migration
AU  - Vítor Yang
AU  - Cristian Marchant
AU  - Bing Liu
AU  - Mariana Osswald
AU  - Jesus Lopez-Gay
AU  - Yohanns Bellaïche
AU  - Xiaobo Wang
AU  - Eurico Morais-De-Sá
PY  - 2026
DA  - 2026/06/01
JO  - Journal of Cell Biology
DO  - 10.1083/jcb.202511004
UR  - https://hal.science/hal-05767951v1
AB  - The Rho family GTPases RhoA, Rac1, and Cdc42 are well-established regulators of collective migration by driving the formation of cellular protrusions and by regulating actomyosin contraction and adhesion. However, how their activation and inhibition are spatially and temporally coordinated remains unclear. Using GFP knock-in lines, we systematically characterized the localization patterns of all Drosophila RhoGEFs (activators) and RhoGAPs (inhibitors) in border cells, an in vivo model of collective migration. We have further combined RNAi screening with GFP-based validation of depletion efficiency to assess the functional significance of those RhoGEFs/GAPs expressed in border cells. This identified RhoGAP15B as a localized inhibitor of RhoA activity at the border cell cortex. RhoGAP15B regulates cluster morphology and is enriched at the leading cell front, where it restrains actomyosin contractility to promote protrusive behavior. Our findings reveal RhoGAP15B as a key spatial RhoA regulator and highlight that patterned RhoGAP and RhoGEF activities are essential for coordinating cortical contraction and protrusion dynamics during collective migration.
SN  - 0021-9525
SN  - 1540-8140
ER  -