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J. Cell Biol. 170 (4): 619-626

Copyright © 2005 by the Rockefeller University Press.

Article

Reaching out for signals

filopodia sense EGF and respond by directed retrograde transport of activated receptors

Diane S. Lidke, Keith A. Lidke, Bernd Rieger, Thomas M. Jovin, , and Donna J. Arndt-Jovin

Department of Molecular Biology, Max Planck Institute for Biophysical Chemistry, 37077 Goettingen, Germany

Correspondence to D.S. Lidke: dlidke{at}gwdg.de; or D.J. Arndt-Jovin: djovin{at}gwdg.de

Abstract: ErbB1 receptors situated on cellular filopodia undergo systematic retrograde transport after binding of the epidermal growth factor (EGF) and activation of the receptor tyrosine kinase. Specific inhibitors of the erbB1 receptor tyrosine kinase as well as cytochalasin D, a disruptor of the actin cytoskeleton, abolish transport but not free diffusion of the receptor–ligand complex. Diffusion constants and transport rates were determined with single molecule sensitivity by tracking receptors labeled with EGF conjugated to fluorescent quantum dots. Retrograde transport precedes receptor endocytosis, which occurs at the base of the filopodia. Initiation of transport requires the interaction and concerted activation of at least two liganded receptors and proceeds at a constant rate mediated by association with actin. These findings suggest a mechanism by which filopodia detect the presence and concentration of effector molecules far from the cell body and mediate cellular responses via directed transport of activated receptors.

B. Rieger's present address is FEI Electron Optics, 5600 KA Eindhoven, Netherlands.

Abbreviations used in this paper: FRET, fluorescence resonance energy transfer; MSD, mean square displacement; QD, quantum dot; RMSD, root MSD.

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