Nuclear pore complex integrity requires Lnp1, a regulator of cortical endoplasmic reticulum.
Nuclear pore complex integrity requires Lnp1, a regulator of cortical endoplasmic reticulum.
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DOI：
10.1091/mbc.e15-01-0053
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发表时间：
2015-08-01
影响因子：
3.3
通讯作者：
Wente SR
中科院分区：
文献类型：
--
作者：
Casey AK;Chen S;Novick P;Ferro-Novick S;Wente SR
核膜和内质网是同一连续膜系统的一部分，具有共同的进化历史。遗传，细胞生物学和生化数据的组合被用来确定作用的皮质ER蛋白LNP 1和Sey1在核孔复合物的稳定性在芽殖酵母。核膜（NE）和内质网（ER）是同一连续膜系统的组成部分，但具有不同的细胞功能。越来越多的证据表明，一些ER蛋白在NE中的作用是正确的核孔复合物（NPC）结构和功能。在这项研究中，我们确定了NE的作用，在酿酒酵母LNP 1和Sey1，蛋白质所需的适当皮质ER的形成。lnp1Δ和sey1Δ突变体都表现出与编码关键NPC结构组分的基因突变体的合成遗传相互作用。Lnp1和Sey1都与其他已经确定NPC角色的ER组分（包括Rtn1，Yop1，Pom33和Per33）物理关联。有趣的是，lnp 1 Δ rtn 1 Δ突变体而不是rtn 1 Δ sey 1 Δ突变体在NPC分布中表现出缺陷。此外，在Sey1不存在的情况下，必需的NPC组装因子Ndc1改变了相互作用。Lnp 1通过其C末端锌指基序在体外二聚化，这是正确的ER结构所需的特性，但不是NPC完整性所需的特性。这些发现表明，Lnp1在NPC完整性中的作用与ER中的功能是分离的，并且与Ndc1和Rtn1相互作用有关。
The nuclear envelope and endoplasmic reticulum (ER) are part of the same contiguous membrane system and have a common evolutionary history. A combination of genetic, cell biological, and biochemical data is used to identify roles for the cortical ER proteins Lnp1 and Sey1 in nuclear pore complex stability in budding yeast. 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.