- Casey AK, Chen S, Novick P, Ferro-Novick S, Wente SR. Nuclear pore complex integrity requires Lnp1, a regulator of cortical ER. Molecular biology of the cell. 2015 Jun 3. PMID: 26041935 [PubMed].
The nuclear envelope (NE) and endoplasmic reticulum (ER) are components of the same contiguous membrane system yet harbor distinct cellular functions. Mounting evidence suggests roles for some ER proteins in the NE for proper nuclear pore complex (NPC) structure and function. In this study, we identify a NE role in Saccharomyces cerevisiae for Lnp1 and Sey1, proteins required for proper cortical ER formation. Both lnp1Δ and sey1Δ mutants exhibit synthetic genetic interactions with mutants in genes encoding key NPC structural components. Both Lnp1 and Sey1 physically associate with other ER components that have established NPC roles including Rtn1, Yop1, Pom33, and Per33. Interestingly, lnp1Δ rtn1Δ mutants but not rtn1Δ sey1Δ mutants exhibit defects in NPC distribution. Furthermore, the essential NPC assembly factor Ndc1 has altered interactions in the absence of Sey1. Lnp1 dimerizes in vitro via its C-terminal zinc-finger motif, a property that is required for proper ER structure but not NPC integrity. These findings suggest that Lnp1's role in NPC integrity is separable from functions in the ER and is linked to Ndc1 and Rtn1 interactions.