Nuclear pore complex structure and assembly involve the ER membrane protein Rtn1

Abstract

Nucleocytoplasmic transport occurs exclusively through nuclear pore complexes (NPCs) which have been implicated in proper embryonic development. Although structural studies have resolved the complex NPC architecture, the mechanism that directs pore membrane fusion and NPC biogenesis remains unclear. Reticulons (RTNs) and Yop1/DP1 are conserved membrane protein families required to form and maintain the tubular endoplasmic reticulum (ER). Remarkably, whereas NPC membrane proteins such as Pom34 and Pom152 are not required for viability, an rtn1δ yop1δ pom34δ pom152δ quadruple null (δ) mutant is lethal. This suggests that Rtn1 and/or Yop1 play a role in NPC structure, assembly and/or maintenance. This lethality is rescued by expression of wild type RTN1, as well as by the more nuclear localized point mutant rtn1‐K48I. The exogenous expression of RTN1 and rtn1‐K48I also rescues a lethal pom34δ nup59δ double mutant. Nup59 is a structural NPC protein linked to NPC assembly. These results indicate that Rtn1 has at least a partial redundancy in function with NPC structural and transmembrane proteins. In addition, this suggests a function for the reticulons at the NE that is independent of RTNs role at the tubular ER. We hypothesize that RTNs and/or Yop1/DP1 stabilize the membrane curvature of the nuclear pore during NPC assembly.Grant Funding SourceIRACDA and NIH