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Volume 17, Number 14, Issue of July 15, 1997 pp. 5445-5454
Copyright ©1997 Society for NeuroscienceThe trkA Receptor Mediates Growth Cone Turning toward a Localized Source of Nerve Growth Factor
Received March 18, 1997; revised May 5, 1997; accepted May 7, 1997.
Gianluca Gallo1, Frances B. Lefcort2, and Paul C. Letourneau1 1 Department of Cell Biology and Neuroanatomy, University of Minnesota, Minneapolis, Minnesota 55455, and 2 Department of Biology, Montana State University, Bozeman, Montana 59717
We have developed an in vitro system for studying the interaction of chick dorsal root ganglion neuronal growth cones with a localized source of nerve growth factor (NGF) covalently conjugated to polystyrene beads. Growth cones rapidly turned and migrated under NGF-coated beads in a process that involved the initial formation of persistent contact with a bead, followed by directed flow of cytoplasm toward the point of contact. A role for the local activation of the high-affinity NGF receptor trkA was suggested by a strong inhibition of the turning response by (1) the addition of an antibody against the extracellular portion of trkA, (2) the elevation of the background concentration of NGF to saturate trkA, or (3) the presence of a concentration of the drug K252a that inhibits trkA activation. NGF binding to the pan-neurotrophin receptor p75 is also involved but is not required for turning. These data show a new role for both the trkA and the p75 receptors: the mediation of local events in the guidance of nerve growth cones.
Key words: growth cone; nerve growth factor; trkA; p75; guidance; filopodia
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