BAR scaffolds drive membrane fission by crowding disordered domains

Wilton T. Snead; Wade F. Zeno; Grace Kago; Ryan W. Perkins; J Blair Richter; Chi Zhao; Eileen M. Lafer; Jeanne C. Stachowiak

Here we report that membrane scaffolding by BAR domains works synergistically with steric pressure among bulky disordered domains to drive membrane fission. By highlighting the ability of BAR scaffolds to locally concentrate disordered domains, this work helps to explain how steric pressure can be generated and locally sustained at membrane surfaces. Further, our findings are in contrast with the established view that BAR scaffolds prevent fission by stabilizing membrane tubes (Boucrot et al., 2012) . Instead, our work suggests that BAR proteins that contain substantial disordered regions are more likely to be drivers of membrane fission. In support of this idea, previous work showed that the yeast amphiphysins Rvs161/167 are essential for membrane fission, and deletion of these proteins leads to a defect in the entry of clathrin-coated pits into cells (Kaksonen et al., 2005; Kishimoto et al., 2011) . Depletion of amphiphysin by RNA interference also dramatically inhibits clathrin-mediated endocytosis in mammalian cells (Meinecke et al., 2013) , although this endocytic defect has been attributed to a reduction in dynamin recruitment.