Reaching out for signals: filopodia sense EGF and respond by directed retrograde transport of activated receptors.
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.
Lidke
Diane S
DS
Department of Molecular Biology, Max Planck Institute for Biophysical Chemistry, 37077, Goettingen, Germany. dlidke@gwdg.de
Lidke
Keith A
KA
Rieger
Bernd
B
Jovin
Thomas M
TM
Arndt-Jovin
Donna J
DJ
D008841:Actin Cytoskeleton / Q000378:metabolism; D001692:Biological Transport / Q000187:drug effects; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D004058:Diffusion / Q000187:drug effects; D019281:Dimerization; D004705:Endocytosis / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D036681:Fluorescence Recovery After Photobleaching; D006801:Humans; D008024:Ligands; D008954:Models, Biological; D011485:Protein Binding / Q000187:drug effects; D020836:Protein Structure, Quaternary; D011554:Pseudopodia / Q000187:drug effects* / Q000378:metabolism*; D045663:Quantum Dots; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*
D004791:Enzyme Inhibitors; D008024:Ligands; D011993:Recombinant Fusion Proteins; D004815:Epidermal Growth Factor; D066246:ErbB Receptors