Department of Cell Biology, Yale University School of Medicine, New Haven, CT, USA.
Department of Biomedical Engineering, Yale University, New Haven, CT, USA.
J Cell Biol. 2023 Oct 2;222(10). doi: 10.1083/jcb.202301112. Epub 2023 Jul 26.
The endoplasmic reticulum's (ER's) 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 the 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.
内质网（ER）的结构与其众多功能直接相关，但内质网的形成过程尚不完全清楚。我们研究了内质网膜弯曲蛋白 reticulon 4（Rtn4）如何定位并在膜中组织，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。我们的数据进一步表明，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 低聚物呈线性形状，包含大约五个拷贝的蛋白质，并且优先沿小管轴平行取向。我们的观察结果支持这样一种机制，即寡聚化导致每个分子的局部 Rtn4 浓度增加，通过发夹楔入机制增加膜曲率。这种对 Rtn4 的定量分析及其对 ER 膜的影响导致了与 Rtn4 相关的小管形状的新模型。
