Nature Biotechnology22, 198 - 203 (2004)
Published online: 4 January 2004; | doi:10.1038/nbt929
Quantum dot ligands provide new insights into erbB/HER receptor−mediated signal transduction
Diane S Lidke1, Peter Nagy1, Rainer Heintzmann1, Donna J Arndt-Jovin1, Janine N Post1, Hernan E Grecco2, Elizabeth A Jares-Erijman3
& Thomas M Jovin1
1
Department of Molecular Biology, Max Planck Institute for Biophysical Chemistry, Am Fassberg 11, D-37077 Göttingen, Germany.
2
Laboratorio de Electrónica Cuántica, Departamento de Física, Facultad de Ciencias Exactas y Naturales, Intendente Güiraldes 2160, Pabellón I, Ciudad Universitaria, Universidad de Buenos Aires, C1428EHA Buenos Aires, Argentina.
3
Departamento de Química Orgánica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Pabellón II 3er piso, Ciudad Universitaria, C1428EHA Buenos Aires, Argentina.
The erbB/HER family of transmembrane receptor tyrosine kinases (RTKs) mediate cellular responses to epidermal growth factor (EGF) and related ligands. We have imaged the early stages of RTK-dependent signaling in living cells using: (i) stable expression of erbB1/2/3 fused with visible fluorescent proteins (VFPs), (ii) fluorescent quantum dots (QDs) bearing epidermal growth factor (EGF-QD) and (iii) continuous confocal laser scanning microscopy and flow cytometry. Here we demonstrate that EGF-QDs are highly specific and potent in the binding and activation of the EGF receptor (erbB1), being rapidly internalized into endosomes that exhibit active trafficking and extensive fusion. EGF-QDs bound to erbB1 expressed on filopodia revealed a previously unreported mechanism of retrograde transport to the cell body. When erbB2-monomeric yellow fluorescent protein (mYFP) or erbB3-monomeric Citrine (mCitrine) were coexpressed with erbB1, the rates and extent of endocytosis of EGF-QD and the RTK-VFP demonstrated that erbB2 but not erbB3 heterodimerizes with erbB1 after EGF stimulation, thereby modulating EGF-induced signaling. QD-ligands will find widespread use in basic research and biotechnological developments.
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