Cargo binding promotes KDEL receptor clustering at the mammalian cell surface
Abstract
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 puzzling. In an attempt to fill this gap we followed a combined experimental and theoretical approach by dissecting and modulating cargo binding, internalization and cellular response mediated by KDEL receptors (KDELRs) at the mammalian cell surface after interaction with a model cargo/ligand. Using a fluorescent variant of ricin toxin A chain as KDELR-ligand (eGFP-RTAH/KDEL), we demonstrate that cargo binding induces dose-dependent receptor cluster formation at and subsequent internalization from the membrane which is associated and counteracted by anterograde and microtubule-assisted receptor transport to preferred docking sites at the plasma membrane. By means of analytical arguments and extensive numerical simulations we show that cargo-synchronized receptor transport from and to the membrane is causative for KDELR/cargo cluster formation at the mammalian cell surface.
- Publication:
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Scientific Reports
- Pub Date:
- June 2016
- DOI:
- 10.1038/srep28940
- arXiv:
- arXiv:1712.06151
- Bibcode:
- 2016NatSR...628940B
- Keywords:
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- Quantitative Biology - Subcellular Processes;
- Condensed Matter - Soft Condensed Matter;
- Physics - Biological Physics
- E-Print:
- 11 pages, 5 figures