Trafficking of a Ligand-Receptor Complex on the Growth Cones as an Essential Step for the Uptake of Nerve Growth Factor at the Distal End of the Axon: A Single-Molecule Analysis
Open Access
- 2 March 2005
- journal article
- research article
- Published by Society for Neuroscience in Journal of Neuroscience
- Vol. 25 (9), 2181-2191
- https://doi.org/10.1523/jneurosci.4570-04.2005
Abstract
The behavior of single molecules of neurotrophins on growth cones was observed by the use of the fluorescent conjugate of nerve growth factor (NGF), Cy3-NGF. After the application of 0.4 nmCy3-NGF, chick dorsal root ganglion growth cones responded within 1 min of adding the stimulus by expanding their lamellipodia. Only 40 molecules of Cy3-NGF, which occupied 2s-1. The behavior of Cy3-NGF was shifted to a one-directional rearward movement toward the central region of the growth cone. The one-directional movement of Cy3-NGF displayed the same rate as the rearward flow of actin, ∼4 μm/min. This movement could be stopped by the application of the potent inhibitor of actin polymerization, latrunculin B. Molecules of Cy3-NGF were suggested to be internalized in the vicinity of the central region of the growth cone during this rearward trafficking, because Cy3-NGF remained in the growth cone after the growth cones had been exposed to an acidic surrounding medium: acidic medium causes the complete dissociation of Cy3-NGF from the receptors on the surface of growth cones. These results suggested that actin-driven trafficking of the NGF receptor complex is an essential step for the accumulation and endocytosis of NGF at the growth cone and for the retrograde transport of NGF toward the cell body.Keywords
This publication has 34 references indexed in Scilit:
- NGF-Induced Axon Growth Is Mediated by Localized Inactivation of GSK-3β and Functions of the Microtubule Plus End Binding Protein APCNeuron, 2004
- Nerve Growth Factor Processing and Trafficking Events Following TrkA-Mediated EndocytosisEndocrinology, 1998
- The Molecular Biology of Axon GuidanceScience, 1996
- Myosin Drives Retrograde F-Actin Flow in Neuronal Growth ConesNeuron, 1996
- Growth cone advance is inversely proportional to retrograde F-actin flowNeuron, 1995
- Flow Cytometric Analysis of Fluorescein-Labeled Nerve Growth Factor Binding to A875 Human Melanoma CellsExperimental Cell Research, 1994
- The trk Proto-Oncogene Product: a Signal Transducing Receptor for Nerve Growth FactorScience, 1991
- Actions of cytochalasins on the organization of actin filaments and microtubules in a neuronal growth cone.The Journal of cell biology, 1988
- Developmental Neurobiology and the Natural History of Nerve Growth FactorAnnual Review of Neuroscience, 1982
- Cell-substrate contacts illuminated by total internal reflection fluorescence.The Journal of cell biology, 1981