Figure 8. The role of Brl1 during nuclear pore complex (NPC) assembly.

(A) Brl1 (red) enriches on the inside of NPC maturation intermediates and promotes inner nuclear membrane–outer nuclear membrane (INM-ONM) fusion through the membrane-binding amphipathic helix (AH) motif and likely in cooperation with Brr6 (yellow). (B) If Brl1 cannot reach the critical concentration required to promote membrane fusion, unresolved nuclear envelope (NE) herniations, filled with electron-dense material, appear. (C) Overexpressed Brl1(I395D) with a perturbed AH (blue) concentrates at the NPC assembly site. It remodels the NE membranes and leads to expanded multilayered herniations but ultimately fails to induce membrane fusion. (D) Brl1 at the INM can only physically interact with Brr6 or Brl1 at the ONM when the NE leaflets approach as it is the case at NPC assembly sites. Dimensions based on our cryo-electron tomography (cryo-ET) data (Figure 3—figure supplement 1D), structure prediction (Figure 5—figure supplement 1), and measurements of the NE (Appendix 1—figure 2B).