Open AccessLow Intensity Pulsed Ultrasound (LIPUS) promotes cell motility through vinculin-controlled Rac1 GTPase activity
Author(s) -
Paul Atherton,
Franziska Lausecker,
Andrew Harrison,
Christoph Ballestrem
Publication year - 2017
Publication title -
journal of cell science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.384
H-Index - 278
eISSN - 1477-9137
pISSN - 0021-9533
DOI - 10.1242/jcs.192781
Subject(s) - vinculin , focal adhesion , microbiology and biotechnology , biology , fibronectin , actin cytoskeleton , endocytosis , cytoskeleton , actin , vitronectin , cell migration , low intensity pulsed ultrasound , cell adhesion , extracellular matrix , cell , signal transduction , biochemistry , medicine , ultrasound , radiology , therapeutic ultrasound
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 Rac activation associated with dramatic actin cytoskeleton rearrangements. Our study demonstrates that the mechanosensitive focal adhesion (FA) protein vinculin and both Focal Adhesion Kinase (FAK) and Rab5 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 Rac induction and actin rearrangements but 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 Rac signalling events. Together our data show that LIPUS is sensed by cell-matrix adhesions through vinculin, which in turn modulates a Rab5-Rac pathway to control ultrasound-mediated endocytosis and cell motility. Finally, we demonstrate that a similar FAK-Rab5-Rac pathway acts to control cell spreading upon fibronectin.