Paxillin controls directional cell motility in response to physical cues. Cell Adh Migr 2012;6(6):502-8
Date
10/19/2012Pubmed ID
23076140Pubmed Central ID
PMC3547894DOI
10.4161/cam.21672Scopus ID
2-s2.0-84872070258 (requires institutional sign-in at Scopus site) 19 CitationsAbstract
Physical cues from the extracellular environment that influence cell shape and directional migration are transduced into changes in cytoskeletal organization and biochemistry through integrin-based cell adhesions to extracellular matrix (ECM). Paxillin is a focal adhesion (FA) scaffold protein that mediates integrin anchorage to the cytoskeleton, and has been implicated in regulation of FA assembly and cell migration. To determine whether paxillin is involved in coupling mechanical distortion with directional movement, cell shape was physically constrained by culturing cells on square-shaped fibronectin-coated adhesive islands surrounded by non-adhesive barrier regions that were created with a microcontact printing technique. Square-shaped cells preferentially formed FAs and extended lamellipodia from their corner regions when stimulated with PDGF, and loss of paxillin resulted in loss of this polarized response. Selective expression of the N- and C-terminal domains of paxillin produced opposite, but complementary, effects on suppressing or promoting lamellipodia formation in different regions of square cells, which corresponded to directional motility defects in vitro. Paxillin loss or mutation was also shown to affect the formation of circular dorsal ruffles, and this corresponded to changes in cell invasive behavior in 3D. This commentary addresses the implications of these findings in terms of how a multifunctional FA scaffold protein can link physical cues to cell adhesion, protrusion and membrane trafficking so as to control directional migration in 2D and 3D. We also discuss how microengineered ECM islands and in vivo model systems can be used to further elucidate the functions of paxillin in directional migration.
Author List
Sero JE, German AE, Mammoto A, Ingber DEAuthor
Akiko Mammoto PhD, MD Associate Professor in the Pediatrics department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsCell Membrane
Cell Movement
Cell Polarity
Cell Shape
Cells, Cultured
Cytoskeleton
Extracellular Matrix
Fibroblasts
Focal Adhesions
Humans
Mice
Models, Biological
Mutation
Paxillin
Platelet-Derived Growth Factor
Pseudopodia
