SigmaR1 shapes rough endoplasmic reticulum membrane sheets,Developmental Cell

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SigmaR1 shapes rough endoplasmic reticulum membrane sheets
Developmental Cell ( IF 10.7 ) Pub Date : 2024-07-05 , DOI: 10.1016/j.devcel.2024.06.005
Eric M Sawyer ₁ , Liv E Jensen ₂ , Janet B Meehl ₁ , Kevin P Larsen ₂ , Daniel A Petito ₁ , James H Hurley ₃ , Gia K Voeltz ₁

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Rough endoplasmic reticulum (ER) sheets are a fundamental domain of the ER and the gateway into the secretory pathway. Although reticulon proteins stabilize high-curvature ER tubules, it is unclear whether other proteins scaffold the flat membranes of rough ER sheets. Through a proteomics screen using ER sheet-localized RNA-binding proteins as bait, we identify the sigma-1 receptor (SigmaR1) as an ER sheet-shaping factor. High-resolution live cell imaging and electron tomography assign SigmaR1 as an ER sheet-localized factor whose levels determine the amount of rough ER sheets in cells. Structure-guided mutagenesis and in vitro reconstitution on giant unilamellar vesicles further support a mechanism whereby SigmaR1 oligomers use their extended arrays of amphipathic helices to bind and flatten the lumenal leaflet of ER membranes to oppose membrane curvature and stabilize rough ER sheets.

中文翻译：

SigmaR1 塑造粗糙的内质网膜片

粗面内质网（ER）片是 ER 的基本结构域，也是进入分泌途径的门户。尽管网状蛋白稳定高曲率 ER 小管，但尚不清楚其他蛋白质是否支撑粗糙 ER 片的平板膜。通过使用 ER 片定位的 RNA 结合蛋白作为诱饵的蛋白质组学筛选，我们将 sigma-1 受体（SigmaR1）鉴定为 ER 片形成因子。高分辨率活细胞成像和电子断层扫描将 SigmaR1 指定为 ER 片定位因子，其水平决定了细胞中粗糙 ER 片的数量。结构引导的诱变和在巨大的单层囊泡上的体外重建进一步支持一种机制，即 SigmaR1 寡聚体使用其延伸的两亲性螺旋阵列来结合和压平 ER 膜的管腔小叶，以对抗膜曲率并稳定粗糙的 ER 片。

更新日期：2024-07-05

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