Low-intensity pulsed ultrasound promotes cell motility through vinculin-controlled Rac1 GTPase activity

J Cell Sci. 2017 Jul 15;130(14):2277-2291. doi: 10.1242/jcs.192781. Epub 2017 Jun 2.


Low-intensity pulsed ultrasound (LIPUS) is a therapy used clinically to promote healing. Using live-cell imaging we show that LIPUS stimulation, acting through integrin-mediated cell-matrix adhesions, rapidly induces Rac1 activation associated with dramatic actin cytoskeleton rearrangements. Our study demonstrates that the mechanosensitive focal adhesion (FA) protein vinculin, and both focal adhesion kinase (FAK, also known as PTK2) and Rab5 (both the Rab5a and Rab5b isoforms) have key roles in regulating these effects. Inhibiting the link of vinculin to the actin-cytoskeleton abolished LIPUS sensing. We show that this vinculin-mediated link was not only critical for Rac1 induction and actin rearrangements, but was also important for the induction of a Rab5-dependent increase in the number of early endosomes. Expression of dominant-negative Rab5, or inhibition of endocytosis with dynasore, also blocked LIPUS-induced Rac1 signalling events. Taken together, our data show that LIPUS is sensed by cell matrix adhesions through vinculin, which in turn modulates a Rab5-Rac1 pathway to control ultrasound-mediated endocytosis and cell motility. Finally, we demonstrate that a similar FAK-Rab5-Rac1 pathway acts to control cell spreading upon fibronectin.

Keywords: Endocytosis; LIPUS; Migration; Rac1; Vinculin.

MeSH terms

  • 3T3 Cells
  • Actins / metabolism
  • Animals
  • Cell Movement / radiation effects*
  • Endocytosis / physiology
  • Endocytosis / radiation effects
  • Enzyme Activation / radiation effects
  • Fibronectins / metabolism
  • Focal Adhesion Kinase 1 / metabolism
  • Melanoma, Experimental / metabolism
  • Melanoma, Experimental / pathology
  • Mice
  • Neuropeptides / metabolism*
  • Ultrasonic Waves
  • Vinculin / metabolism*
  • rab5 GTP-Binding Proteins / metabolism
  • rac1 GTP-Binding Protein / metabolism*


  • Actins
  • Fibronectins
  • Neuropeptides
  • Rac1 protein, mouse
  • Vinculin
  • Focal Adhesion Kinase 1
  • Ptk2 protein, mouse
  • rab5 GTP-Binding Proteins
  • rac1 GTP-Binding Protein