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Redox Biol., Mar 26 2025, 82 S2213-2317(25)00131-4 | https://doi.org/10.1016/j.redox.2025.103618
Coronin 1a-mediated F-actin disassembly controls effector function in murine neutrophils
Anton Shaverskyi a, Jan Hegermann c, Korbinian Brand b, Kyeong-Hee Lee a,1, Niko Föger a,1
aInflammation Research Group, Institute of Clinical Chemistry, Hannover Medical School, Hannover, Germany
bInstitute of Clinical Chemistry, Hannover Medical School, Hannover, Germany
cCentral Research Facility Electron Microscopy, Hannover Medical School, Hannover, Germany
1K.-H.L. and N.F. shared senior authorship.
Corresponding authors : Kyeong-Hee Lee, Niko Föger
aInflammation Research Group, Institute of Clinical Chemistry, Hannover Medical School, Hannover, Germany
bInstitute of Clinical Chemistry, Hannover Medical School, Hannover, Germany
cCentral Research Facility Electron Microscopy, Hannover Medical School, Hannover, Germany
1K.-H.L. and N.F. shared senior authorship.
Corresponding authors : Kyeong-Hee Lee, Niko Föger
Abstract
The double-edged role of neutrophils in effective host defense and harmful pathology is an emerging topic in clinical research. Neutrophils release highly potent antimicrobial granule compounds and reactive oxygen species (ROS) that can also be detrimental to the host and promote inflammatory diseases and cancer. Here we show that disassembly of F-actin greatly facilitates ROS production and degranulation in neutrophils. Utilizing neutrophils from Coronin 1a (Coro1a)-deficient mice, our data reveal that the actin-regulatory protein Coro1a controls this spatial F-actin deconstruction and concomitantly forms a signaling complex with Rac-GTPases, thereby promoting activation and translocation of Rac to the membrane during neutrophil activation. This functional activity of Coro1a was critical for neutrophil granule exocytosis and the activation of the NADPH oxidase complex. Consistent with these findings, impaired ROS production in Coro1a-deficient neutrophils was rescued by pharmacological promotion of actin depolymerization or activation of Rac. Together, our findings suggest that the Coro1a/Rac signaling hub acts as a central regulatory element that coordinates actin cytoskeletal reorganization required for the execution of neutrophil effector functions. Since Coro1a is highly conserved between mice and humans and associated with human immunodeficiency, our results are also relevant for human biomedical studies.
논문정보
- Research article
- 2025년 03월 (BRIC 등록일 2025-04-02)
- 국외 연구진
- 바이오·의료융합 > 다학제 융합/복합
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