Runz Heiko, Miura Kota, Weiss Matthias, Pepperkok Rainer
Cell Biology & Cell Biophysics Programme, European Molecular Biology Laboratory, EMBL, Heidelberg, Germany.
EMBO J. 2006 Jul 12;25(13):2953-65. doi: 10.1038/sj.emboj.7601205. Epub 2006 Jun 22.
Alterations in endoplasmic reticulum (ER) cholesterol are fundamental for a variety of cellular processes such as the regulation of lipid homeostasis or efficient protein degradation. We show that reduced levels of cellular sterols cause a delayed ER-to-Golgi transport of the secretory cargo membrane protein ts-O45-G and a relocation to the ER of an endogenous protein cycling between the ER and the Golgi complex. Transport inhibition is characterized by a delay in the accumulation of ts-O45-G in ER-exit sites (ERES) and correlates with a reduced mobility of ts-O45-G within ER membranes. A simple mathematical model describing the kinetics of ER-exit predicts that reduced cargo loading to ERES and not the reduced mobility of ts-O45-G accounts for the delayed ER-exit and arrival at the Golgi. Consistent with this, membrane turnover of the COPII component Sec23p is delayed in sterol-depleted cells. Altogether, our results demonstrate the importance of sterol levels in COPII mediated ER-export.
内质网（ER）胆固醇的改变对于多种细胞过程至关重要，如脂质稳态的调节或有效的蛋白质降解。我们发现细胞固醇水平降低会导致分泌性货物膜蛋白ts-O45-G从内质网到高尔基体的运输延迟，以及一种在内质网和高尔基体复合体之间循环的内源性蛋白质重新定位到内质网。运输抑制的特征是ts-O45-G在内质网出口位点（ERES）的积累延迟，并且与ts-O45-G在内质网膜内的流动性降低相关。一个描述内质网出口动力学的简单数学模型预测，货物装载到ERES减少而非ts-O45-G的流动性降低导致了内质网出口延迟和到达高尔基体的延迟。与此一致的是，COPII组分Sec23p的膜周转在固醇缺乏的细胞中延迟。总之，我们的结果证明了固醇水平在COPII介导的内质网输出中的重要性。
