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Volume 17, Number 14,
Issue of July 15, 1997
pp. 5445-5454
Copyright ©1997 Society for Neuroscience
The 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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