An endosomal tether undergoes an entropic collapse to bring vesicles together

Within cells, Rab GTPase proteins recruit tethering effectors that allow transport vesicles to dock and fuse with their target membranes. This raises the question of how the long, rod-like tethering molecules such as the protein EEA1 can capture vesicles, yet allow the reduction of the distance between the membranes for fusion. Marino Zerial and colleagues address this question by reconstituting an endosomal tethering machinery consisting of EEA1, membranes and vesicles carrying Rab5. They find that, in a new role, Rab5:GTP induces a change in EEA1 conformation from extended to flexible, allowing it to bend. In addition, they show that membrane tethering by EEA1:Rab5:GTP generates a force that also helps to bring two membranes together.