Interaction of Paxillin with Poly(A)-Binding Protein 1 and Its Role in Focal Adhesion Turnover and Cell Migration

We have previously identified poly(A)-binding protein 1 (PABP1) as a ligand for paxillin and shown that the paxillin-PABP1 complex undergoes nucleocytoplasmic shuttling. By targeting the paxillin-binding subdomain sequences in PABP1, we have generated mutants of PABP1 that do not bind to cellular paxillin. Here we report that paxillin association is necessary for efficient nuclear export of PABP1 and that RNA interference of paxillin drives the nuclear accumulation of PABP1. Furthermore, ablation of paxillin-PABP1 association impeded a number of indices of cell motility including spreading on fibronectin, cell migration on two-dimensional matrices, and transmigration in Boyden chambers. These data indicate that PABP1 must asso-ciate with paxillin in order to be efficiently transported from the nucleus to the cytoplasm and that this event is necessary for cells to remodel their focal adhesions during cell migration. The leading edge or lamellipodium of migrating cells is the point at which integrins engage the extracellular matrix, an interaction that leads to integrin clustering into an array of small multiprotein focal complexes (31) containing an array of structural and signaling proteins that act to establish and main-tain the polarity of the migrating cell. The 68-kDa protei