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 associate 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.
Woods
Alison J
AJ
Department of Biochemistry, University of Leicester, University Road, Leicester LE1 7 RH, United Kingdom.
Kantidakis
Theodoros
T
Sabe
Hisataka
H
Critchley
David R
DR
Norman
Jim C
JC
D021581:Active Transport, Cell Nucleus / Q000502:physiology; D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D002465:Cell Movement / Q000502:physiology*; D002467:Cell Nucleus / Q000737:chemistry / Q000378:metabolism; D003593:Cytoplasm / Q000737:chemistry; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D005347:Fibroblasts / Q000378:metabolism; D022001:Focal Adhesions / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D051419:Paxillin; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D039122:Poly(A)-Binding Protein I / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D034622:RNA Interference; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D014162:Transfection
D003598:Cytoskeletal Proteins; C496061:PXN protein, human; D051419:Paxillin; D010750:Phosphoproteins; D039122:Poly(A)-Binding Protein I; C496062:Pxn protein, mouse; D012333:RNA, Messenger