Molecular and Cell Biology, Department of Biosciences and Center of Human and Molecular Biology (ZHMB), Saarland University, Saarbrücken, Germany.
Department of Theoretical Physics and Center for Biophysics, Saarland University, Saarbrücken, Germany.
PLoS One. 2020 Jul 9;15(7):e0235864. doi: 10.1371/journal.pone.0235864. eCollection 2020.
In eukaryotic cells, KDEL receptors (KDELRs) facilitate the retrieval of endoplasmic reticulum (ER) luminal proteins from the Golgi compartment back to the ER. Apart from the well-documented retention function, recent findings reveal that the cellular KDELRs have more complex roles, e.g. in cell signalling, protein secretion, cell adhesion and tumorigenesis. Furthermore, several studies suggest that a sub-population of KDELRs is located at the cell surface, where they could form and internalize KDELR/cargo clusters after K/HDEL-ligand binding. However, so far it has been unclear whether there are species- or cell-type-specific differences in KDELR clustering. By comparing ligand-induced KDELR clustering in different mouse and human cell lines via live cell imaging, we show that macrophage cell lines from both species do not develop any clusters. Using RT-qPCR experiments and numerical analysis, we address the role of KDELR expression as well as endocytosis and exocytosis rates on the receptor clustering at the plasma membrane and discuss how the efficiency of directed transport to preferred docking sites on the membrane influences the exponent of the power-law distribution of the cluster size.
在真核细胞中，KDEL 受体（KDELRs）有助于将内质网（ER）腔蛋白从高尔基体区室中回收回 ER。除了众所周知的保留功能外，最近的发现揭示了细胞 KDELR 具有更复杂的作用，例如在细胞信号转导、蛋白质分泌、细胞黏附和肿瘤发生中。此外，一些研究表明，KDELR 的亚群位于细胞表面，在那里它们可以在 K/HDEL-配体结合后形成和内化 KDELR/货物簇。然而，到目前为止，还不清楚 KDELR 聚类是否存在物种或细胞类型特异性差异。通过通过活细胞成像比较不同的小鼠和人类细胞系中配体诱导的 KDELR 聚类，我们表明来自两种物种的巨噬细胞系都不会形成任何簇。通过 RT-qPCR 实验和数值分析，我们探讨了 KDELR 表达以及内吞和胞吐率对质膜上受体聚类的作用，并讨论了定向运输到膜上首选停靠位点的效率如何影响簇大小的幂律分布的指数。
