Paxillin?s Nuclear Transport depends upon Focal Adhesion Dynamics and Interactions with the LD4 Binding Region of FAT Domains

Abstract

The nuclear transport of paxillin appears critical for paxillin function but the mechanism of transport remains unclear. We show that the nuclear transport of paxillin is tuned by focal adhesion turnover and the presence of FAT domains. Focal adhesion turnover was controlled using triangular or circular fibronectin islands. Focal adhesion turnover and nuclear transport of paxillin increased in circles relative to triangles. Paxillin point mutations had no effect nuclear transport. Knocking out FAK and vinculin increased nuclear paxillin. This was reversible by rescue with WT FAK but not if the FAT domain of FAK was mutated to inhibit paxillin binding. Expressing just the FAT domain not only brought down nuclear levels of paxillin but FRAP studies indicated a high immobile fraction at focal adhesions. Taken together, focal adhesion turnover and FAT domains regulate nuclear localization of paxillin, suggesting possible roles for transcriptional control through paxillin by focal adhesions.