Spatiotemporal regulation of Mst1 by RAPL is critical for lymphocyte polarity and adhesion

Abstract

RAPL, a Rap1-binding protein is required for efficient immune cell trafficking. Here, we identify mammalian Ste20-like kinase Mst1 as a critical effector of RAPL. RAPL regulates the localization and kinase activity of Mst1. MST1 knockdown demonstrates its requirement for the induction of both a polarized morphology and LFA-1 clustering and adhesion triggered by chemokines and TCR ligation. RAPL and Mst1 localized to vesicular compartments and dynamically translocated with LFA-1 to the leading edge by Rap1 activation, suggesting the regulatory role of RAPL-Mst1 complex in intracellular transport of LFA-1. Our study reveals a novel function for Mst1, relaying the Rap1-RAPL signal to produce the cell polarity and adhesion of lymphocytes.