Caveolae play a crucial role in regulating mechanotransduction by responding to changes in membrane tension. In the context of cell rear retraction during migration, caveolae are involved in a feedback loop with RhoA/ROCK1 signaling. When membrane tension is low, caveolae formation at the cell rear is promoted, which is dependent on RhoA/ROCK1 signaling, Ect2, and PKN2. This leads to F-actin alignment, actomyosin contractility, and rapid rear retraction. Loss of caveolae, increased membrane tension, or inhibition of Rho signaling disrupt this positive feedback loop, inhibiting rear retraction and impeding cell migration.
The molecular mechanisms by which caveolae regulate the activities of Ect2, ROCK, and ARHGAP29 involve a dynamic interplay between these proteins. ROCK is recruited to caveolae at high membrane tension, and its activity is required for caveolae reassembly after hypo-osmotic shock. On the other hand, ARHGAP29, a RhoGAP, is associated with caveolae at low membrane tension and inhibits caveolae rear localization and cell migration when overexpressed. This suggests that Ect2/ROCK and ARHGAP29 have opposing functions in caveolae formation and actomyosin contractility at the cell rear. The spatio-temporal coordination of these proteins allows for the regulation of cycles of caveolae assembly/disassembly and actomyosin contractility, ultimately influencing cell rear retraction during migration.