REEP4 is recruited to the inner nuclear membrane by ELYS and promotes nuclear pore complex formation

Abstract

Nuclear pore complexes (NPCs) are channels within the nuclear envelope that mediate nucleocytoplasmic transport. NPCs assemble either into the closed nuclear envelope during interphase or concomitantly with nuclear envelope reformation during anaphase. Both, interphase and post-mitotic NPC biogenesis require local deformation of membrane. Yet, the factors that control proper membrane remodeling for post-mitotic NPC assembly are unknown. Here, we report that the reticulon homology domain-protein REEP4 localizes not only to high-curvature membrane of the cytoplasmic endoplasmic reticulum (ER) but also to the inner nuclear membrane (INM). We show that REEP4 is recruited to the INM by the NPC biogenesis factor ELYS and promotes NPC assembly. REEP4 contributes mainly to anaphase NPC assembly, suggesting that REEP4 has an unexpected role in coordinating nuclear envelope reformation with post-mitotic NPC biogenesis.

Mitotic disassembly and reassembly of nuclear pore complexes

“…This involves binding of the transmembrane nucleoporin POM121 to the Y-complex and of NDC1 to NUP53 [14,20], which initiates reassembly of the inner NPC ring. The ER membrane protein REEP4 is also suggested to cooperate with ELYS in mitotic NPC assembly [55]. Because REEP4 stabilizes highly curved membranes, the ELYS-REEP4 axis could establish a link between chromatin-associated NPC assembly intermediates and the curved membrane topology at the NPC assembly site.…”

“…How microtubules influence the mode of NE reformation is unclear because they seem not to impede the general access of membranes to chromatin. The presence of microtubules in the core region might influence ER membrane topology, which could in turn affect NPC assembly [55,77]. However, an alternative model suggests that a gradient of Aurora B kinase activity, originating at the midzone, delays NE and NPC assembly on lagging chromosomesand probably also in the midzone-oriented core region of the main nucleus [78,79].…”