Cell-type-specific differences in KDEL receptor clustering in mammalian cells

PLoS One. 2020 Jul 9;15(7):e0235864. doi: 10.1371/journal.pone.0235864. eCollection 2020.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Cell Membrane / metabolism
  • Endocytosis
  • Exocytosis
  • Gene Expression
  • Humans
  • Macrophages / metabolism
  • Mice
  • Protein Transport
  • RNA, Messenger / analysis
  • RNA, Messenger / genetics
  • Receptors, Peptide / analysis
  • Receptors, Peptide / genetics
  • Receptors, Peptide / metabolism*
  • Vesicular Transport Proteins / analysis
  • Vesicular Transport Proteins / genetics
  • Vesicular Transport Proteins / metabolism*

Substances

  • KDELR1 protein, human
  • RNA, Messenger
  • Receptors, Peptide
  • Vesicular Transport Proteins
  • KDELR2 protein, human

Grants and funding

This work was funded by the Deutsche Forschungsgemeinschaft (DFG) through Collaborative Research Center SFB 1027. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.