Flood Julia R, Mendina Caitlin A, Audhya Anjon
Department of Biomolecular Chemistry, University of Wisconsin School of Medicine and Public Health, Madison, WI, 53706, USA.
Department of Biomolecular Chemistry, University of Wisconsin School of Medicine and Public Health, Madison, WI, 53706, USA.
Curr Opin Cell Biol. 2025 Jun;94:102492. doi: 10.1016/j.ceb.2025.102492. Epub 2025 Mar 10.
The early secretory pathway governs the transport of thousands of secreted and transmembrane proteins and lipids from the endoplasmic reticulum (ER) to juxtaposed ER-Golgi Intermediate Compartments (ERGIC). This process is largely directed by Coat Protein complex II (COPII), which accumulates on distinct, ribosome-free ER subdomains (transitional ER) to generate highly curved transport intermediates of various sizes and shapes. The rate of secretory flux from the ER can vary significantly, depending on cell type, environmental cues, and other factors, but the mechanisms that regulate COPII-mediated trafficking have been slow to emerge. Here, we focus on recent progress that has contributed to our understanding of how the early secretory pathway is structured to facilitate the export of cargoes from the ER into a chasm approximately 300-500-nm in size, prior to fusion with ERGIC membranes without the aid of cytoskeletal elements to guide their journey.
早期分泌途径负责将数千种分泌蛋白、跨膜蛋白和脂质从内质网（ER）运输到相邻的内质网-高尔基体中间腔室（ERGIC）。这一过程在很大程度上由II型被膜小泡蛋白复合体（COPII）引导，COPII在内质网特定的无核糖体亚结构域（过渡内质网）上聚集，以生成各种大小和形状的高度弯曲的运输中间体。内质网的分泌通量速率会因细胞类型、环境信号及其他因素而有显著差异，但调节COPII介导的运输的机制却迟迟未被揭示。在此，我们聚焦于近期的研究进展，这些进展有助于我们理解早期分泌途径是如何构建的，以便在不借助细胞骨架元件引导运输的情况下，促进货物从内质网输出到一个大小约为300 - 500纳米的间隙中，然后与ERGIC膜融合。
