Fuentes Lukas A, Marin Zach, Tyson Jonathan, Baddeley David, Bewersdorf Joerg
Department of Cell Biology, Yale University School of Medicine, New Haven, CT, USA.
Department of Biomedical Engineering, Yale University, New Haven, CT, USA.
bioRxiv. 2023 Jan 27:2023.01.26.525608. doi: 10.1101/2023.01.26.525608.
The endoplasmic reticulum’s (ER) structure is directly linked to the many functions of the ER but its formation is not fully understood. We investigate how the ER-membrane curving protein reticulon 4 (Rtn4) localizes to and organizes in the membrane and how that affects local ER structure. We show a strong correlation between the local Rtn4 density and the local ER membrane curvature. Our data further reveal that the typical ER tubule possesses an elliptical cross-section with Rtn4 enriched at either end of the major axis. Rtn4 oligomers are linear-shaped, contain about five copies of the protein, and preferentially orient parallel to the tubule axis. Our observations support a mechanism in which oligomerization leads to an increase of the local Rtn4 concentration with each molecule increasing membrane curvature through a hairpin wedging mechanism. This quantitative analysis of Rtn4 and its effects on the ER membrane result in a new model of tubule shape as it relates to Rtn4.
Rtn4 forms linear-shaped oligomers that contain an average of five Rtn4 proteins, localize to the sides of elliptical tubules, prefer orientations near parallel to the tubule axis, and increase local curvature of the ER membrane by increasing local Rtn4 density.
内质网（ER）的结构与内质网的多种功能直接相关，但其形成过程尚未完全明晰。我们研究内质网膜弯曲蛋白网织蛋白4（Rtn4）如何定位于膜并在膜中组织排列，以及这如何影响局部内质网结构。我们发现局部Rtn4密度与局部内质网膜曲率之间存在很强的相关性。我们的数据进一步揭示，典型的内质网小管具有椭圆形横截面，Rtn4在长轴的两端富集。Rtn4寡聚体呈线性形状，包含约五个蛋白拷贝，并且优先平行于小管轴定向。我们的观察结果支持一种机制，即寡聚化导致局部Rtn4浓度增加，每个分子通过发夹楔入机制增加膜曲率。对Rtn4及其对内质网膜的影响进行的这种定量分析得出了一种与Rtn4相关的小管形状新模型。
Rtn4形成平均包含五个Rtn4蛋白的线性寡聚体，定位于椭圆形小管的侧面，优先平行于小管轴定向，并通过增加局部Rtn4密度增加内质网膜的局部曲率。
