A role for the juxtamembrane cytoplasm in the molecular dynamics of focal adhesions

PLoS One. 2009;4(1):e4304. doi: 10.1371/journal.pone.0004304. Epub 2009 Jan 28.

Abstract

Focal adhesions (FAs) are specialized membrane-associated multi-protein complexes that link the cell to the extracellular matrix and play crucial roles in cell-matrix sensing. Considerable information is available on the complex molecular composition of these sites, yet the regulation of FA dynamics is largely unknown. Based on a combination of FRAP studies in live cells, with in silico simulations and mathematical modeling, we show that the FA plaque proteins paxillin and vinculin exist in four dynamic states: an immobile FA-bound fraction, an FA-associated fraction undergoing exchange, a juxtamembrane fraction experiencing attenuated diffusion, and a fast-diffusing cytoplasmic pool. The juxtamembrane region surrounding FAs displays a gradient of FA plaque proteins with respect to both concentration and dynamics. Based on these findings, we propose a new model for the regulation of FA dynamics in which this juxtamembrane domain acts as an intermediary layer, enabling an efficient regulation of FA formation and reorganization.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Computer Simulation
  • Cytoplasm / metabolism*
  • Diffusion
  • Fluorescence Recovery After Photobleaching
  • Focal Adhesions / metabolism*
  • HeLa Cells
  • Humans
  • Integrin beta3 / metabolism
  • Paxillin / metabolism
  • Rats
  • Vinculin / metabolism

Substances

  • Integrin beta3
  • Paxillin
  • Vinculin