Figure 8.

Model showing steps required for Rvs-mediated membrane scission during the endocytosis process with rvs161 rvs167 BAR domain mutants overlaid on the steps for which they are defective. The model is partially adapted from Liu et al., 2009. Pulling forces generated by actin polymerization impinge on the selected endocytic site and invaginate the membrane. BAR domain proteins form helical structures at the neck of the invaginating plasma membrane. The N-terminal amphipathic helix and positive charges on the surface (concave and loop region) of the Rvs BAR domain are required for this step. At the plasma membrane, complex sphingolipids are needed for Rvs167 localization to the endocytic sites. Next, Rvs161-Rvs167 and synaptojanin function to promote scission of the vesicle, by Rvs protecting the PI(4,5)P₂ in the vesicle neck and Inp52 hydrolyzing PI(4,5)P₂ to generate a lipid phase boundary. This reaction leads to a mechanochemical feedback loop, which creates a large interfacial force, driving membrane scission (Liu et al., 2006, 2009). The RC RC BAR domain mutant is specifically defective at this stage.