Endoplasmic reticulum–plasma membrane contact gradients direct cell migration

Directed cell migration is driven by the front–back polarization of intracellular signalling. Receptor tyrosine kinases and other inputs activate local signals that trigger membrane protrusions at the front. Equally important is a long-range inhibitory mechanism that suppresses signalling at the back to prevent the formation of multiple fronts. However, the identity of this mechanism is unknown. Here we report that endoplasmic reticulum–plasma membrane (ER–PM) contact sites are polarized in single and collectively migrating cells. …