Cargo binding promotes KDEL receptor clustering at the mammalian cell surface

  title={Cargo binding promotes KDEL receptor clustering at the mammalian cell surface},
  author={Bj{\"o}rn Becker and M. Reza Shaebani and Domenik Rammo and Tobias Bubel and Ludger Santen and Manfred J. Schmitt},
  journal={Scientific Reports},
Transmembrane receptor clustering is a ubiquitous phenomenon in pro- and eukaryotic cells to physically sense receptor/ligand interactions and subsequently translate an exogenous signal into a cellular response. Despite that receptor cluster formation has been described for a wide variety of receptors, ranging from chemotactic receptors in bacteria to growth factor and neurotransmitter receptors in mammalian cells, a mechanistic understanding of the underlying molecular processes is still… 

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

By comparing ligand-induced KDELR clustering in different mouse and human cell lines via live cell imaging, it is shown that macrophage cell lines from both species do not develop any clusters.

KDEL receptor is a cell surface receptor that cycles between the plasma membrane and the Golgi via clathrin-mediated transport carriers

The results indicate that surface-expressed KDEL receptor undergoes highly complex recycling pathways via the Golgi and peri-nuclear recycling endosomes that are positive for Rab11 and Rab14, respectively, and appears to preferentially utilize clathrin-mediated endocytic pathway as well as clathrifying transport carriers for export from the trans -Golgi network.

H/KDEL receptors mediate host cell intoxication by a viral A/B toxin in yeast

Yeast H/KDEL receptor Erd2p is identified as membrane receptor of K28, a viral A/B toxin carrying an HDEL motif at its cell binding β-subunit which ensures retrograde toxin transport through the secretory pathway of a target cell.

KDEL Receptor 1 Contributes to Cell Surface Association of Protein Disulfide Isomerases.

  • A. BartelsS. Göttert I. Lorenzen
  • Biology
    Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology
  • 2019
It is shown that the C-terminal KDEL ER retention sequence is sufficient to prevent secretion of PDIA6 into the extracellular space but is mandatory for its association with the cell surface.

The KDEL receptor signalling cascade targets focal adhesion kinase on focal adhesions and invadopodia

Evidence is provided that membrane trafficking activates KDEL receptor and the Src family kinases at focal adhesions of HeLa cells, where this phosphorylates ADP-ribosylation factor GTPase-activating protein with SH3 domain, ankyrin repeat and PH domain (ASAP)1 and focal adhesion kinase (FAK).

Transcriptomics of a KDELR1 knockout cell line reveals modulated cell adhesion properties

Impaired adhesion capacity of KDELR1-KO cells was further demonstrated through in vitro adhesion assays, while collagen- and/or laminin-coating nearly doubled the adhesion property of KD ELR1 -KO cells compared to wild-type, confirming a transcriptional adaptation to improve or restore the cellular adhesion capability.

KDEL Receptors: Pathophysiological Functions, Therapeutic Options, and Biotechnological Opportunities

KDEL receptors can be considered potential targets for the development of novel therapeutic strategies for a variety of diseases involving proteostasis disruption, cancer progression, and infectious disease, but no drugs targeting KDELR functions are available to date.

A modified cholera toxin B subunit containing an ER retention motif enhances colon epithelial repair via an unfolded protein response

  • J. RoyalY. Oh N. Matoba
  • Biology, Medicine
    FASEB journal : official publication of the Federation of American Societies for Experimental Biology
  • 2019
CTB‐KDEL exhibits unique wound healing effects in the colon that are mediated by its localization to the ER and subsequent activation of UPR in epithelial cells, and implications for a novel therapeutic approach for mucosal healing, a significant unmet need in IBD treatment.

Photoactivatable Hsp47: A Tool to Regulate Collagen Secretion and Assembly

It is envisioned that photoactivatable Hsp47 allows unprecedented fundamental studies of collagen biosynthesis, matrix biology, and inspires new therapeutic concepts in biomedicine and tissue regeneration.

The Function of KDEL Receptors as UPR Genes in Disease

This review will discuss the emerging connection between UPR activation and KDEL receptors as it pertains to ER proteostasis and disease states.



Anthrax toxin triggers endocytosis of its receptor via a lipid raft–mediated clathrin-dependent process

It is found that although endocytosis of ATR is slow, clustering it into rafts either via PA heptamerization or using an antibody sandwich is necessary and sufficient to trigger efficient internalization and allow delivery of LF to the cytoplasm.

Minimal Mesoscale Model for Protein-Mediated Vesiculation in Clathrin-Dependent Endocytosis

A minimal mesoscale model is presented which quantitatively explains several experimental observations on the process of vesicle nucleation induced by the clathrin-coated assembly prior to vesicles scission inClathrin dependent endocytosis.

Outside-in signaling – a brief review of GPCR signaling with a focus on the Drosophila GPCR family

Findings that the Drosophila odorant and gustatory receptors are not bona fide GPCRs as is the case for their mammalian counterparts are discussed and a phylogenetic analysis of the bona fide Drosophile GPCR families is presented that suggest potential roles for several family members.

The Epidermal Growth Factor Receptor (EGFR) Promotes Uptake of Influenza A Viruses (IAV) into Host Cells

First indications for an interplay of IAV with receptor tyrosine kinases (RTKs) with representative RTK family-members the epidermal growth factor receptor (EGFR) and the c-Met receptor were studied, showing that these receptors transmit entry relevant signals upon virus binding.

EphB/ephrinB Signaling in Cell Adhesion and Migration

The EphBs and ephrinBs are specifically localized and modified to promote higher-order clustering and initiate of bidirectional signaling in cell adhesion and migration.

Endocytotic uptake and retrograde transport of a virally encoded killer toxin in yeast

We demonstrate that a virally encoded yeast ‘killer’ toxin is entering its eukaryotic target cell by endocytosis, subsequently travelling the yeast secretory pathway in reverse to exhibit its lethal

Receptor Pre-Clustering and T cell Responses: Insights into Molecular Mechanisms

A mathematical model is formulated to characterize the pre-clustering of T cell receptors (TCRs) on the surface of T cells, motivated by the experimentally observed distribution of TCR clusters on thesurface of naive and memory T cells and shows that pre-Clustering reduces the mean activation time.

Mechanics of receptor-mediated endocytosis.

It is shown that particles in the size range of tens to hundreds of nanometers can enter or exit cells via wrapping even in the absence of clathrin or caveolin coats, and an optimal particles size exists for the smallest wrapping time.