Single particle tracking reveals that EGFR signaling activity is amplified in clathrin-coated pits
Autor(en): | Ibach, J. Radon, Y. Gelléri, M. Sonntag, M.H. Brunsveld, L. Bastiaens, P.I.H. Verveer, P.J. |
Stichwörter: | epidermal growth factor receptor, 79079-06-4; Clathrin; Ligands; Receptor, Epidermal Growth Factor; epidermal growth factor receptor; clathrin; epidermal growth factor receptor; ligand, Article; autophosphorylation; binding affinity; carboxy terminal sequence; cellular distribution; clathrin coated pit; controlled study; cross phosphorylation; dimerization; investigative procedures; ligand binding; membrane biology; molecular dynamics; phosphotyrosine binding domain; protein aggregation; protein domain; protein localization; protein phosphorylation; signal transduction; single particle tracking; structure activity relation; cluster analysis; coated pit; confocal microscopy; human; MCF-7 cell line; metabolism; phosphorylation; signal transduction, Clathrin; Cluster Analysis; Coated Pits, Cell-Membrane; Humans; Ligands; MCF-7 Cells; Microscopy, Confocal; Phosphorylation; Receptor, Epidermal Growth Factor; Signal Transduction | Erscheinungsdatum: | 2015 | Herausgeber: | Public Library of Science | Journal: | PLoS ONE | Volumen: | 10 | Ausgabe: | 11 | Zusammenfassung: | Signaling from the epidermal growth factor receptor (EGFR) via phosphorylation on its Cterminal tyrosine residues requires self-association, which depends on the diffusional properties of the receptor and its density in the plasma membrane. Dimerization is a key event for EGFR activation, but the role of higher order clustering is unknown. We employed single particle tracking to relate the mobility and aggregation of EGFR to its signaling activity. EGFR mobility alternates between short-lived free, confined and immobile states. In the immobile state, EGFR tends to aggregate in clathrin-coated pits, which is further enhanced in a phosphorylation-dependent manner and does not require ligand binding. EGFR phosphorylation is further amplified by cross-phosphorylation in clathrin-coated pits. Because phosphorylated receptors can escape from the pits, local gradients of signaling active EGFR are formed. These results show that amplification of EGFR phosphorylation by receptor clustering in clathrin-coated pits supports signal activation at the plasma membrane. © 2015 Ibach et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source arecredited. |
ISSN: | 19326203 | DOI: | 10.1371/journal.pone.0143162 | Externe URL: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-84956632142&doi=10.1371%2fjournal.pone.0143162&partnerID=40&md5=f61d22c534406601d90f503534b971c9 |
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