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Volume 17, Number 18,
Issue of September 15, 1997
pp. 7007-7016
Copyright ©1997 Society for Neuroscience
Trk Receptors Function As Rapid Retrograde Signal Carriers in the
Adult Nervous System
Received April 30, 1997; revised June 26, 1997; accepted July 1, 1997.
Anita Bhattacharyya1,
Fiona L. Watson2,
Tatum A. Bradlee1,
Scott L. Pomeroy3,
Charles D. Stiles1, and
Rosalind A. Segal2
1 Dana-Farber Cancer Institute and Department of
Microbiology and Molecular Genetics, Harvard Medical School, Boston,
Massachusetts 02115, 2 Department of Neurology, Beth
Israel-Deaconess Medical Center and Program in Neuroscience, Harvard
Medical School, Boston, Massachusetts 02115, and 3 Division
of Neuroscience, Department of Neurology, Children's Hospital, and
Program in Neuroscience, Harvard Medical School, Boston, Massachusetts
02115
During development target-derived neurotrophins promote the
survival of neurons. However, mature neurons no longer depend on the
target for survival. Do target-derived neurotrophins retain retrograde
signaling functions in mature neurons, and, if so, how are they
executed? We addressed this question by using a
phosphotyrosine-directed antibody to locate activated Trk receptors in
adult rat sciatic nerve. We show that catalytically active Trk
receptors are located within the axon of adult rat sciatic nerve and
that they are distributed throughout the length of the axons. These
catalytically active receptors are phosphorylated on tyrosine at a
position that couples them to the signal-generating proteins Ras and
PI3 kinase. Neurotrophin applied at sciatic nerve terminals increases
both catalytic activity and phosphorylation state of Trk receptors at
distant points within the axons. Trk activation initiated at the nerve
terminals propagates through the axon toward the nerve cell body at an
initial rate that exceeds that of conventional vesicular transport.
However, our data suggest that this rapid signal is nevertheless
vesicle-associated. Thus, in mature nerves, activated Trk receptors
function as rapid retrograde signal carriers to execute remote
responses to target-derived neurotrophins.
Key words:
neurotrophin;
Trk;
sciatic nerve;
receptor tyrosine
kinase;
signal transduction
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