Actin cortex formation is required for integrin clustering but not activation during leukocyte adhesion.
5 affiliations
- 1Department of Immunology, School of Medicine, UConn Health, 263 Farmington Ave., Farmington, Connecticut 06030, USA.
- 2Academy of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, 1200 Cai Lun Road, Shanghai 201203, China.
- 3Department of Biochemistry and Molecular Biology and Department of Pathology, University of Texas Medical Branch, 301 University Blvd, Galveston, Texas 77555, USA.
- 4Center for Cell Analysis and Modeling, UConn Health, 263 Farmington Ave., Farmington, Connecticut 06030, USA.
- 5Department of Pediatrics, Yale School of Medicine, New Haven, Connecticut 06510, USA.
Abstract
Leukocyte recruitment is critical for tissue homeostasis and inflammatory responses. Chemokine-induced β₂ integrin-dependent adhesion is the first and most critical step of leukocyte recruitment. Previous studies have shown that crosstalk between integrins and the actin cytoskeleton is vital for the migration of adherent leukocytes. However, whether and how the actin cytoskeleton contributes to integrin-dependent leukocyte adhesion remains poorly defined. As we recently demonstrated, a defect in integrin clustering, even in the presence of normal integrin activation, is sufficient to cause an adhesion defect in cystic fibrosis monocytes. Interestingly, these defects were accompanied by a concomitant deficiency in actin cortex formation, suggesting that actin cortex formation specifically facilitates integrin clustering rather than activation. In this study, we test this hypothesis by using the pharmacological actin polymerization inhibitor cytochalasin D (CytoD) in both human and mouse monocytes. Interestingly, we found that CytoD selectively impaired chemokine-induced actin cortex formation, yet had no impact on the total amount of polymerized F-actin. Using super-resolution microscopy, we found that inhibiting actin cortex formation directly suppressed integrin clustering but not integrin activation. Cells with inhibited actin cortex formation prevented Coronin 1A (CORO1A) binding to integrins, suggesting that the actin cortex is critical for CORO1A recruitment to integrins and thereby facilitates integrin clustering. Expanding beyond the integrin-activation-centric leukocyte adhesion paradigm, we underscore the importance of integrin clustering and identify that the actin cortex specifically regulates integrin clustering but not activation. This fundamental finding warrants investigation into selective targeting in the design of therapeutic strategies for inflammation.
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BibTeX
@article{younis2026actin,
title = {{Actin cortex formation is required for integrin clustering but not activation during leukocyte adhesion.}},
author = {Doulathunnisa Ahamed Younis and Raphael Serna and Wei Liu and Beiyan Zhou and Anthony T Vella and Liang Hu and Yunfeng Chen and Ji Yu and Emanuela M Bruscia and Zhichao Fan},
journal = {International journal of biological sciences},
year = {2026},
month = sep,
doi = {10.7150/ijbs.137102},
url = {https://europepmc.org/article/MED/42909899},
note = {CC BY},
}
RIS
TY - JOUR
TI - Actin cortex formation is required for integrin clustering but not activation during leukocyte adhesion.
AU - Doulathunnisa Ahamed Younis
AU - Raphael Serna
AU - Wei Liu
AU - Beiyan Zhou
AU - Anthony T Vella
AU - Liang Hu
AU - Yunfeng Chen
AU - Ji Yu
AU - Emanuela M Bruscia
AU - Zhichao Fan
PY - 2026
DA - 2026/09/10
JO - International journal of biological sciences
DO - 10.7150/ijbs.137102
UR - https://europepmc.org/article/MED/42909899
AB - Leukocyte recruitment is critical for tissue homeostasis and inflammatory responses. Chemokine-induced β₂ integrin-dependent adhesion is the first and most critical step of leukocyte recruitment. Previous studies have shown that crosstalk between integrins and the actin cytoskeleton is vital for the migration of adherent leukocytes. However, whether and how the actin cytoskeleton contributes to integrin-dependent leukocyte adhesion remains poorly defined. As we recently demonstrated, a defect in integrin clustering, even in the presence of normal integrin activation, is sufficient to cause an adhesion defect in cystic fibrosis monocytes. Interestingly, these defects were accompanied by a concomitant deficiency in actin cortex formation, suggesting that actin cortex formation specifically facilitates integrin clustering rather than activation. In this study, we test this hypothesis by using the pharmacological actin polymerization inhibitor cytochalasin D (CytoD) in both human and mouse monocytes. Interestingly, we found that CytoD selectively impaired chemokine-induced actin cortex formation, yet had no impact on the total amount of polymerized F-actin. Using super-resolution microscopy, we found that inhibiting actin cortex formation directly suppressed integrin clustering but not integrin activation. Cells with inhibited actin cortex formation prevented Coronin 1A (CORO1A) binding to integrins, suggesting that the actin cortex is critical for CORO1A recruitment to integrins and thereby facilitates integrin clustering. Expanding beyond the integrin-activation-centric leukocyte adhesion paradigm, we underscore the importance of integrin clustering and identify that the actin cortex specifically regulates integrin clustering but not activation. This fundamental finding warrants investigation into selective targeting in the design of therapeutic strategies for inflammation.
SN - 1449-2288
ER -