MARCKS-related protein regulates cytoskeletal organization at cell-cell and cell-substrate contacts in epithelial cells

Abstract

MARCKS-related protein (MRP) is tagged by biotin ligase fused to occludin and the level of tagging increases ∼20-fold following IFN/TNF treatment. GFP-MRP is focused at the lateral cell membrane and its overexpression potentiates the physiological response of the tight junction barrier to cytokines. However, deletion of MRP does not abrogate cytokine responses, suggesting that MRP is not required in the occludin-dependent IFN/TNF response. Instead, our results reveal a key role for MRP in epithelial cells in control of multiple actin-based structures, likely by regulation of integrin signaling. Changes in focal adhesion organization and basal actin stress fibers in MRP KO are reminiscent of those seen FAK KO cells. In addition, we find alterations in cell-cell interactions in MRP KO cells that are associated with increased junctional tension, suggesting that MRP may play a role in focal adhesion/adherens junction cross talk. Together, our results are consistent with a key role for MRP in cytoskeletal organization of cell contacts in epithelial cells.