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J. Biol. Chem., Vol. 277, Issue 45, 43160-43167, November 8, 2002
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From the Brain-derived neurotrophic factor (BDNF)
signaling through its receptor TRKB modulates survival,
differentiation, and activity of neurons. BDNF activates TRKB on the
cell surface, which leads to the initiation of intracellular signaling
cascades and different biological responses in neurons. Neuronal
activity has been shown to regulate TRKB levels on the plasma membrane
of neurons, but little is known about other factors affecting TRKB
surface expression levels. We report here that BDNF regulates the cell
surface levels of transfected or endogenously expressed full-length
TRKB, depending on the exposure time in neuroblastoma cells and primary
hippocampal neurons. BDNF rapidly increases TRKB surface expression
levels in seconds, whereas treatment of cells with BDNF for a longer time (minutes to hours) leads to decreased TRKB surface levels. Coexpression of the full-length TRKB together with the
truncated TRKB.T1 isoform results in decreased levels of
full-length TRKB on the cell surface. This effect is specific to the T1
isoform, because coexpression of a kinase-dead TRKB mutant or another
kinase domain-lacking TRKB form, truncated T-Shc, leads to increased TRKB surface levels. Our results suggest that regulation of TRKB surface expression levels by different factors is tightly controlled by
complex mechanisms in active neurons.
Regulation of TRKB Surface Expression by Brain-derived
Neurotrophic Factor and Truncated TRKB Isoforms*
§,,,,, and
**
Department of Neurobiology, A. I. Virtanen
Institute and Department of Psychiatry, University of Kuopio,
P. O. Box 1627, 70211 Kuopio, Finland and ¶ Universiteat
Erlangen, Institute of Biochemistry, Fahrstrasse 17, 91054 Erlangen, Germany
*
This work was supported by the Academy of Finland, the
Sigrid Juselius Foundation, and the European Union.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.
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