Cargo binding promotes KDEL receptor clustering at the mammalian cell surface

Björn Becker, M. Reza Shaebani, Domenik Rammo, Tobias Bubel, Ludger Santen, Manfred J. Schmitt*

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

19 Citations (Scopus)

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.

Original languageEnglish
Article number28940
JournalScientific Reports
Volume6
DOIs
Publication statusPublished - 29 Jun 2016
Externally publishedYes

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