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a role for the juxtamembrane cytoplasm in the molecular dynamics of focal adhesions近膜胞浆的作用的分子动力学焦点粘连.pdf

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a role for the juxtamembrane cytoplasm in the molecular dynamics of focal adhesions近膜胞浆的作用的分子动力学焦点粘连

A Role for the Juxtamembrane Cytoplasm in the Molecular Dynamics of Focal Adhesions 1 2 1 2,3 1 4 Haguy Wolfenson , Ariel Lubelski , Tamar Regev , Joseph Klafter , Yoav I. Henis *, Benjamin Geiger * 1 Department of Neurobiology, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel, 2 School of Chemistry, Sackler Faculty of Exact Sciences, Tel Aviv University, Tel Aviv, Israel, 3 Freiburg Institute for Advanced Studies (FRIAS), University of Freiburg, Freiburg, Germany, 4 Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel 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. Cit