Nuclear Transport of Paxillin Depends on Myosin Contraction

Abstract

Paxillin is a focal adhesion protein that also shuttles to the nucleus like other Lim domain proteins. If focal adhesions are sites of mechanotransduction, then the movement of paxillin to the nucleus may depend upon the mechanical properties of the matrix and the contractile activity of the cell. Further, translocation of focal adhesion molecules, like paxillin, zyxin and Hic-5, to the nucleus has been implicated in transcriptional control. For example, we find that serum starvation of cells, inhibits movement of paxillin to the nucleus and there is a burst of transport upon serum addition. On a fibronectin matrix, force generation is necessary for nuclear transport. Both inhibition of myosin contraction by blebbistatin and inhibition of actin filament assembly, decreased the rate of paxillin accumulation in the nucleus in the presence of the inhibitor of nuclear export, Leptomycin B. Further, by altering the cell's contractile state using fibronectin micro-patterns, we found dramatic differences in paxillin's nuclear transport rate. On circular patterns where there was greater contraction of the actin network, there was more rapid transport of paxillin. Based upon these findings, we suggest that paxillin movement to the nucleus is part of a mechanosensory function wherein forces at the periphery cause the modification of paxillin that results in its movement to the nucleus where it modifies the transcription profile and eventually cell behavior.