A myristoylated alanine-rich C-kinase substrate (MARCKS) inhibitor peptide attenuates neutrophil outside-in β2-integrin activation and signaling.

MARCKS is an actin and PIP2-binding protein that plays an essential role in neutrophil migration and adhesion; however, the molecular details regarding MARCKS function in these processes remains unclear. Neutrophil adhesion and migration also require the cell surface receptors β₂-integrins. We hypothesized that MARCKS inhibition would alter neutrophil β₂-integrin activation and signaling. We utilized a MARCKS-targeting peptide to inhibit MARCKS in inside-out and outside-in β₂-integrin activation in neutrophils. MANS-mediated MARCKS inhibition had no significant effect on inside-out β₂-integrin activation. MANS treatment significantly attenuated ICAM-1/Mn²⁺-stimulated static adhesion, cell spreading and β₂-integrin clustering, suggesting a role for MARCKS function in outside-in β₂-integrin activation. Additional work is needed to better understand the molecular mechanisms of MARCKS role in outside-in β₂-integrin activation and signaling.