Work

Actin cortex formation is required for integrin clustering but not activation during leukocyte adhesion

Year: 2026

Type: article

Abstract: 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.

Source: International Journal of Biological Sciences

DOI: 10.7150/ijbs.137102