title: Nuclear pore complex integrity requires Lnp1, a regulator of cortical endoplasmic reticulum.
abstract: The nuclear envelope (NE) and endoplasmic reticulum (ER) are components of the same contiguous membrane system and yet have 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. Of interest, 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.
authors.affiliation: Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, TN 37232.
authors.forename: Amanda K
authors.initials: AK
authors.lastname: Casey
authors.affiliation: Department of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, CA 92093.
authors.forename: Shuliang
authors.initials: S
authors.lastname: Chen
authors.affiliation: Department of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, CA 92093 Howard Hughes Medical Institute, University of California at San Diego, La Jolla, CA 92093.
authors.forename: Peter
authors.initials: P
authors.lastname: Novick
authors.affiliation: Department of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, CA 92093.
authors.forename: Susan
authors.initials: S
authors.lastname: Ferro-Novick
authors.affiliation: Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, TN 37232 susan.wente@vanderbilt.edu).
authors.forename: Susan R
authors.initials: SR
authors.lastname: Wente
mesh_terms: D000818:Animals; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism*; D009685:Nuclear Envelope / Q000378:metabolism; D022022:Nuclear Pore / Q000378:metabolism*; D028861:Nuclear Pore Complex Proteins / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D033921:Vesicular Transport Proteins / Q000378:metabolism*
chemical_list: C000607824:Lnp1 protein, S cerevisiae; D008565:Membrane Proteins; D028861:Nuclear Pore Complex Proteins; C472231:SEY1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D033921:Vesicular Transport Proteins