A myristoylated alanine-rich C-kinase substrate (MARCKS) inhibitor peptide attenuates neutrophil outside-in β(2)-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 β(2)-integrins. We hypothesized that MARCKS inhibition would alter neutrophil β(2)-integrin activation and signaling. We utilized a MARCKS-targeting peptide to inhibit MARCKS in inside-out and outside-in β(2)-integrin activation in neutrophils. MANS-mediated MARCKS inhibition had no significant effect on inside-out β(2)-integrin activation. MANS treatment significantly attenuated ICAM-1/Mn(2+)-stimulated static adhesion, cell spreading and β(2)-integrin clustering, suggesting a role for MARCKS function in outside-in β(2)-integrin activation. Additional work is needed to better understand the molecular mechanisms of MARCKS role in outside-in β(2)-integrin activation and signaling.