Abstract
Polarized cell migration is essential for normal organism development and is also a critical component of cancer cell invasion and disease progression. Directional cell motility requires the coordination of dynamic cell-extracellular matrix interactions as well as repositioning of the Golgi apparatus, both of which can be controlled by the microtubule (MT) cytoskeleton. In this paper, we have identified a new and conserved role for the focal adhesion scaffold protein paxillin in regulating the posttranslational modification of the MT cytoskeleton through an inhibitory interaction with the α-tubulin deacetylase HDAC6. We also determined that through HDAC6-dependent regulation of the MT cytoskeleton, paxillin regulates both Golgi organelle integrity and polarized cell invasion and migration in both three-dimensional and two-dimensional matrix microenvironments. Importantly, these data reveal a fundamental role for paxillin in coordinating MT acetylation-dependent cell polarization and migration in both normal and transformed cells.