title: A role for the juxtamembrane cytoplasm in the molecular dynamics of focal adhesions.
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.
authors.affiliation: Department of Neurobiology, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Haguy
authors.initials: H
authors.lastname: Wolfenson
authors.forename: Ariel
authors.initials: A
authors.lastname: Lubelski
authors.forename: Tamar
authors.initials: T
authors.lastname: Regev
authors.forename: Joseph
authors.initials: J
authors.lastname: Klafter
authors.forename: Yoav I
authors.initials: YI
authors.lastname: Henis
authors.forename: Benjamin
authors.initials: B
authors.lastname: Geiger
mesh_terms: D000818:Animals; D003198:Computer Simulation; D003593:Cytoplasm / Q000378:metabolism*; D004058:Diffusion; D036681:Fluorescence Recovery After Photobleaching; D022001:Focal Adhesions / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D039661:Integrin beta3 / Q000378:metabolism; D051419:Paxillin / Q000378:metabolism; D051381:Rats; D016596:Vinculin / Q000378:metabolism
chemical_list: D039661:Integrin beta3; D051419:Paxillin; D016596:Vinculin